Pediatrics

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Cancer patient

Photo by Bill Branson

Brain cancer has overtaken leukemia to become the deadliest childhood cancer in the US, according to a report from the US Centers for Disease Control and Prevention’s National Center for Health Statistics.

The report includes cancer mortality statistics from 1999 to 2014 pertaining to children and adolescents (ages 1 to 19).

In both 1999 and 2014, more than half of all cancer deaths in this population were attributable to leukemias or brain cancers.

In 1999, a greater percentage of deaths were attributed to leukemias than to brain cancers—29.7% and 23.7%, respectively.

But in 2014, brain cancer deaths exceeded leukemia deaths—29.9% and 24.9%, respectively.

The data also showed that, overall, cancer mortality has decreased among children and adolescents in the US.

The cancer death rate was 20% lower in 2014 than in 1999—2.28 deaths per 100,000 persons and 2.85 deaths per 100,000 persons, respectively.

Cancer death rates declined from 1999 to 2014 for all of the age groups studied (divided by 5-year increments) and for both sexes. However, cancer death rates were consistently higher for males than females.

In 2014, 54.8% of cancer deaths among children and adolescents were attributable to either leukemias or brain cancers.

The 2014 death rates by cancer site, from most common to least, were as follows:

• Brain cancers (29.9%)
• Leukemias (24.9%)
• Bone and articular cartilage cancers (10.1%)
• Cancers of the thyroid and other endocrine glands (9.0%)
• Mesothelial and soft tissue cancers (7.7%)
• Non-Hodgkin lymphomas (3.9%)
• Cancers of the liver and intrahepatic bile ducts (2.0%)
• Cancers of the kidney and renal pelvis (1.8%).

Data on the remaining cancer sites were not shown separately.

For more information, see the full report, “Declines in Cancer Death Rates Among Children and Adolescents in the United States, 1999–2014.”

Cancer patient

Photo by Bill Branson

Brain cancer has overtaken leukemia to become the deadliest childhood cancer in the US, according to a report from the US Centers for Disease Control and Prevention’s National Center for Health Statistics.

The report includes cancer mortality statistics from 1999 to 2014 pertaining to children and adolescents (ages 1 to 19).

In both 1999 and 2014, more than half of all cancer deaths in this population were attributable to leukemias or brain cancers.

In 1999, a greater percentage of deaths were attributed to leukemias than to brain cancers—29.7% and 23.7%, respectively.

But in 2014, brain cancer deaths exceeded leukemia deaths—29.9% and 24.9%, respectively.

The data also showed that, overall, cancer mortality has decreased among children and adolescents in the US.

The cancer death rate was 20% lower in 2014 than in 1999—2.28 deaths per 100,000 persons and 2.85 deaths per 100,000 persons, respectively.

Cancer death rates declined from 1999 to 2014 for all of the age groups studied (divided by 5-year increments) and for both sexes. However, cancer death rates were consistently higher for males than females.

In 2014, 54.8% of cancer deaths among children and adolescents were attributable to either leukemias or brain cancers.

The 2014 death rates by cancer site, from most common to least, were as follows:

• Brain cancers (29.9%)
• Leukemias (24.9%)
• Bone and articular cartilage cancers (10.1%)
• Cancers of the thyroid and other endocrine glands (9.0%)
• Mesothelial and soft tissue cancers (7.7%)
• Non-Hodgkin lymphomas (3.9%)
• Cancers of the liver and intrahepatic bile ducts (2.0%)
• Cancers of the kidney and renal pelvis (1.8%).

Data on the remaining cancer sites were not shown separately.

For more information, see the full report, “Declines in Cancer Death Rates Among Children and Adolescents in the United States, 1999–2014.”

Cancer patient

Photo by Bill Branson

Brain cancer has overtaken leukemia to become the deadliest childhood cancer in the US, according to a report from the US Centers for Disease Control and Prevention’s National Center for Health Statistics.

The report includes cancer mortality statistics from 1999 to 2014 pertaining to children and adolescents (ages 1 to 19).

In both 1999 and 2014, more than half of all cancer deaths in this population were attributable to leukemias or brain cancers.

In 1999, a greater percentage of deaths were attributed to leukemias than to brain cancers—29.7% and 23.7%, respectively.

But in 2014, brain cancer deaths exceeded leukemia deaths—29.9% and 24.9%, respectively.

The data also showed that, overall, cancer mortality has decreased among children and adolescents in the US.

The cancer death rate was 20% lower in 2014 than in 1999—2.28 deaths per 100,000 persons and 2.85 deaths per 100,000 persons, respectively.

Cancer death rates declined from 1999 to 2014 for all of the age groups studied (divided by 5-year increments) and for both sexes. However, cancer death rates were consistently higher for males than females.

In 2014, 54.8% of cancer deaths among children and adolescents were attributable to either leukemias or brain cancers.

The 2014 death rates by cancer site, from most common to least, were as follows:

• Brain cancers (29.9%)
• Leukemias (24.9%)
• Bone and articular cartilage cancers (10.1%)
• Cancers of the thyroid and other endocrine glands (9.0%)
• Mesothelial and soft tissue cancers (7.7%)
• Non-Hodgkin lymphomas (3.9%)
• Cancers of the liver and intrahepatic bile ducts (2.0%)
• Cancers of the kidney and renal pelvis (1.8%).

Data on the remaining cancer sites were not shown separately.

For more information, see the full report, “Declines in Cancer Death Rates Among Children and Adolescents in the United States, 1999–2014.”

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

In a commentary about the use of DTC teledermatology in the pediatric arena, the Dermatology Foundation outlined a framework of features needed for such services “to appropriately treat pediatric patients.”

The commentary, by Kavita Sarin, MD, of the department of dermatology, Joyce Teng, MD, of the departments of pediatrics and dermatology, and Alexander L. Fogel, MBA, a medical student at Stanford (Calif.) University, was written on behalf of the Dermatology Foundation in response to the lack of uniform standards and policies governing the use of DTC teledermatology services for pediatric patients.

The writers reported the results of their assessment of the pediatric policies of DTC teledermatology websites and smartphone-based services, which included whether a patient’s age and identity were verified, whether the validity of parental consent was confirmed, and whether any coordination with a patient’s primary care physician or with other physicians occurred.

None of the sites performed all of the features they considered necessary for online pediatric care. “Most services have very minor checks on pediatric access, such as a limit on self-reported age, or a click-box to indicate that parental consent for the visit has been given, and few services allow for medical record capture or coordination with other physicians,” they wrote (J Am Acad Dermatol. 2016 Sep 7. doi: 10.1016/j.jaad.2016.08.002).

Describing the situation as “problematic,” they proposed the framework with features needed for DTC pediatric teledermatology services, which could be “implemented through legislation, regulation, or a third-party certification process,” the researchers wrote.

“We recommend an approach that allows for ample data cross-referencing between patient and parent, and with publicly available records,” to verify identification and parental consent, they noted.

Other elements include the use of standard templates for inputting patient’s medical histories, and sending care plans to the physicians indicated by the parents and patients.

DTC teledermatology “has the potential to offer patients substantial benefits,” but “we must insist on high-quality DTC TD[teledermatology]-services that are coordinated, transparent, focused on quality rather than prescription-writing, and consistent with standards of in-person care,” they wrote.

None of the authors declared any conflicts of interest. Dr. Sarin is supported by a Dermatology Foundation Medical Dermatology Career Development Award.

In a commentary about the use of DTC teledermatology in the pediatric arena, the Dermatology Foundation outlined a framework of features needed for such services “to appropriately treat pediatric patients.”

The commentary, by Kavita Sarin, MD, of the department of dermatology, Joyce Teng, MD, of the departments of pediatrics and dermatology, and Alexander L. Fogel, MBA, a medical student at Stanford (Calif.) University, was written on behalf of the Dermatology Foundation in response to the lack of uniform standards and policies governing the use of DTC teledermatology services for pediatric patients.

The writers reported the results of their assessment of the pediatric policies of DTC teledermatology websites and smartphone-based services, which included whether a patient’s age and identity were verified, whether the validity of parental consent was confirmed, and whether any coordination with a patient’s primary care physician or with other physicians occurred.

None of the sites performed all of the features they considered necessary for online pediatric care. “Most services have very minor checks on pediatric access, such as a limit on self-reported age, or a click-box to indicate that parental consent for the visit has been given, and few services allow for medical record capture or coordination with other physicians,” they wrote (J Am Acad Dermatol. 2016 Sep 7. doi: 10.1016/j.jaad.2016.08.002).

Describing the situation as “problematic,” they proposed the framework with features needed for DTC pediatric teledermatology services, which could be “implemented through legislation, regulation, or a third-party certification process,” the researchers wrote.

“We recommend an approach that allows for ample data cross-referencing between patient and parent, and with publicly available records,” to verify identification and parental consent, they noted.

Other elements include the use of standard templates for inputting patient’s medical histories, and sending care plans to the physicians indicated by the parents and patients.

DTC teledermatology “has the potential to offer patients substantial benefits,” but “we must insist on high-quality DTC TD[teledermatology]-services that are coordinated, transparent, focused on quality rather than prescription-writing, and consistent with standards of in-person care,” they wrote.

None of the authors declared any conflicts of interest. Dr. Sarin is supported by a Dermatology Foundation Medical Dermatology Career Development Award.

In a commentary about the use of DTC teledermatology in the pediatric arena, the Dermatology Foundation outlined a framework of features needed for such services “to appropriately treat pediatric patients.”

The commentary, by Kavita Sarin, MD, of the department of dermatology, Joyce Teng, MD, of the departments of pediatrics and dermatology, and Alexander L. Fogel, MBA, a medical student at Stanford (Calif.) University, was written on behalf of the Dermatology Foundation in response to the lack of uniform standards and policies governing the use of DTC teledermatology services for pediatric patients.

The writers reported the results of their assessment of the pediatric policies of DTC teledermatology websites and smartphone-based services, which included whether a patient’s age and identity were verified, whether the validity of parental consent was confirmed, and whether any coordination with a patient’s primary care physician or with other physicians occurred.

None of the sites performed all of the features they considered necessary for online pediatric care. “Most services have very minor checks on pediatric access, such as a limit on self-reported age, or a click-box to indicate that parental consent for the visit has been given, and few services allow for medical record capture or coordination with other physicians,” they wrote (J Am Acad Dermatol. 2016 Sep 7. doi: 10.1016/j.jaad.2016.08.002).

Describing the situation as “problematic,” they proposed the framework with features needed for DTC pediatric teledermatology services, which could be “implemented through legislation, regulation, or a third-party certification process,” the researchers wrote.

“We recommend an approach that allows for ample data cross-referencing between patient and parent, and with publicly available records,” to verify identification and parental consent, they noted.

Other elements include the use of standard templates for inputting patient’s medical histories, and sending care plans to the physicians indicated by the parents and patients.

DTC teledermatology “has the potential to offer patients substantial benefits,” but “we must insist on high-quality DTC TD[teledermatology]-services that are coordinated, transparent, focused on quality rather than prescription-writing, and consistent with standards of in-person care,” they wrote.

None of the authors declared any conflicts of interest. Dr. Sarin is supported by a Dermatology Foundation Medical Dermatology Career Development Award.

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

dchitnis@frontlinemedcom.com

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

dchitnis@frontlinemedcom.com

A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

©Alexander Traksel/Thinkstock

In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

dchitnis@frontlinemedcom.com

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

Doel nuclear power station

Photo by Rafaël Delaedt

Living near a certain type of nuclear facility may increase a child’s risk of developing acute leukemia, a new study suggests.

The research showed a 2- to 3-fold increased risk of acute leukemia among children living near 1 nuclear facility in Belgium—Mol-Dessel.

However, children who lived near the 3 other Belgian nuclear facilities studied—Doel, Fleurus, and Tihange—had no such increased risk.

Researchers said this study does not confirm a causal relationship between the Mol-Dessel facility and the increased risk of leukemia observed.

However, they did say the facility seems a plausible cause of the increased risk because the data showed significant associations between acute leukemia incidence and 3 surrogate measures of exposure—distance from the facility, prevailing winds, and simulated discharges of the radionuclide Ar-41.

An Van Nieuwenhuyse, MD, PhD, of the Scientific Institute of Public Health in Brussels, Belgium, and colleagues conducted this research and reported the results in the European Journal of Cancer Prevention.

Facilities

The study included 4 nuclear facilities in Belgium—Doel, Mol-Dessel, Fleurus, and Tihange. (The researchers also evaluated a fifth facility, Chooz, but they said it was not possible to draw conclusions regarding this site because the region around it is sparsely populated, which limits the number of cancer cases.)

Doel and Tihange are electricity-generating nuclear power plants that started up in 1975. The nuclear facility at Fleurus has produced radionuclides for medicine and industry since 1971.

The Mol-Dessel facility started up in 1956, and a combination of nuclear activities have taken place there, including scientific and technological research, applied research and metrology, operational waste management, the Belgian Underground Research Laboratory, and the production of fuel assemblies for pressurized-water reactors based on uranium oxide and mixed oxides.

Analysis

The researchers set out to determine whether there was an excess incidence of acute leukemia among children ages 0 to 14 who lived in the vicinity of the aforementioned nuclear facilities. The team analyzed data spanning the period from 2002 to 2008.

For all 4 facilities, the researchers used 2 different measures of surrogate exposure to radionuclide gaseous discharges—residential proximity to the nuclear site and prevailing wind directions.

For the Mol-Dessel site, the researchers also used estimated discharges of the radionuclide Ar-41 as a surrogate measure of exposure.

Results

The data did not show an increased incidence of acute leukemia among children living near the Doel, Tihange, or Fleurus facilities. However, children living within 15 km of the Mol-Dessel site had a significantly increased risk of acute leukemia.

In fact, the researchers said they observed statistically significant associations as a function of distance, prevailing winds, and simulated Ar-41 discharges, which suggests a potential link between acute leukemia incidence and the Mol-Dessel site.

The rate ratios for the Mol-Dessel facility, which were adjusted for age, sex, and socioeconomic status, were:

• 2.70 (95% CI: 1.15–6.33) for children living 0 to 5 km from the site (5 cases of acute leukemia)
• 1.82 (95% CI: 1.02–3.25) for children living 0 to 10 km from the site (11 cases of acute leukemia)
• 1.96 (95% CI: 1.19–3.22) for children living 0 to 15 km from the site (15 cases of acute leukemia)
• 1.09 (95% CI: 0.71–1.61) for children living 0 to 20 km from the site (21 cases of acute leukemia).

The 3 communities lying in the dominant wind direction of the Mol-Dessel nuclear site had rate ratios of 6.81 (95% CI: 2.28–20.32), 4.39 (95% CI: 1.46–13.17), and 3.74 (95% CI: 0.98–14.27).

The researchers calculated P values using Stone’s test, Bithell’s linear risk score test (LRS), and Bithell’s linear risk score test with corresponding ranks as a function of the different measures of surrogate exposure (LRS^r).

All 3 tests showed a significant association between acute leukemia incidence and proximity to the Mol-Dessel site (P<0.01 for all). However, only LRS and LRS^r showed a significant association for wind direction (P=0.01 and 0.03, respectively) and simulated radioactive discharges by Ar-41 (P<0.01 for both).

The researchers noted that, although these results suggest an association between acute childhood leukemia and the Mol-Dessel site, this study had limitations, and more research is needed.

Doel nuclear power station

Photo by Rafaël Delaedt

Living near a certain type of nuclear facility may increase a child’s risk of developing acute leukemia, a new study suggests.

The research showed a 2- to 3-fold increased risk of acute leukemia among children living near 1 nuclear facility in Belgium—Mol-Dessel.

However, children who lived near the 3 other Belgian nuclear facilities studied—Doel, Fleurus, and Tihange—had no such increased risk.

Researchers said this study does not confirm a causal relationship between the Mol-Dessel facility and the increased risk of leukemia observed.

However, they did say the facility seems a plausible cause of the increased risk because the data showed significant associations between acute leukemia incidence and 3 surrogate measures of exposure—distance from the facility, prevailing winds, and simulated discharges of the radionuclide Ar-41.

An Van Nieuwenhuyse, MD, PhD, of the Scientific Institute of Public Health in Brussels, Belgium, and colleagues conducted this research and reported the results in the European Journal of Cancer Prevention.

Facilities

The study included 4 nuclear facilities in Belgium—Doel, Mol-Dessel, Fleurus, and Tihange. (The researchers also evaluated a fifth facility, Chooz, but they said it was not possible to draw conclusions regarding this site because the region around it is sparsely populated, which limits the number of cancer cases.)

Doel and Tihange are electricity-generating nuclear power plants that started up in 1975. The nuclear facility at Fleurus has produced radionuclides for medicine and industry since 1971.

The Mol-Dessel facility started up in 1956, and a combination of nuclear activities have taken place there, including scientific and technological research, applied research and metrology, operational waste management, the Belgian Underground Research Laboratory, and the production of fuel assemblies for pressurized-water reactors based on uranium oxide and mixed oxides.

Analysis

The researchers set out to determine whether there was an excess incidence of acute leukemia among children ages 0 to 14 who lived in the vicinity of the aforementioned nuclear facilities. The team analyzed data spanning the period from 2002 to 2008.

For all 4 facilities, the researchers used 2 different measures of surrogate exposure to radionuclide gaseous discharges—residential proximity to the nuclear site and prevailing wind directions.

For the Mol-Dessel site, the researchers also used estimated discharges of the radionuclide Ar-41 as a surrogate measure of exposure.

Results

The data did not show an increased incidence of acute leukemia among children living near the Doel, Tihange, or Fleurus facilities. However, children living within 15 km of the Mol-Dessel site had a significantly increased risk of acute leukemia.

In fact, the researchers said they observed statistically significant associations as a function of distance, prevailing winds, and simulated Ar-41 discharges, which suggests a potential link between acute leukemia incidence and the Mol-Dessel site.

The rate ratios for the Mol-Dessel facility, which were adjusted for age, sex, and socioeconomic status, were:

• 2.70 (95% CI: 1.15–6.33) for children living 0 to 5 km from the site (5 cases of acute leukemia)
• 1.82 (95% CI: 1.02–3.25) for children living 0 to 10 km from the site (11 cases of acute leukemia)
• 1.96 (95% CI: 1.19–3.22) for children living 0 to 15 km from the site (15 cases of acute leukemia)
• 1.09 (95% CI: 0.71–1.61) for children living 0 to 20 km from the site (21 cases of acute leukemia).

The 3 communities lying in the dominant wind direction of the Mol-Dessel nuclear site had rate ratios of 6.81 (95% CI: 2.28–20.32), 4.39 (95% CI: 1.46–13.17), and 3.74 (95% CI: 0.98–14.27).

The researchers calculated P values using Stone’s test, Bithell’s linear risk score test (LRS), and Bithell’s linear risk score test with corresponding ranks as a function of the different measures of surrogate exposure (LRS^r).

All 3 tests showed a significant association between acute leukemia incidence and proximity to the Mol-Dessel site (P<0.01 for all). However, only LRS and LRS^r showed a significant association for wind direction (P=0.01 and 0.03, respectively) and simulated radioactive discharges by Ar-41 (P<0.01 for both).

The researchers noted that, although these results suggest an association between acute childhood leukemia and the Mol-Dessel site, this study had limitations, and more research is needed.

Doel nuclear power station

Photo by Rafaël Delaedt

Living near a certain type of nuclear facility may increase a child’s risk of developing acute leukemia, a new study suggests.

The research showed a 2- to 3-fold increased risk of acute leukemia among children living near 1 nuclear facility in Belgium—Mol-Dessel.

However, children who lived near the 3 other Belgian nuclear facilities studied—Doel, Fleurus, and Tihange—had no such increased risk.

Researchers said this study does not confirm a causal relationship between the Mol-Dessel facility and the increased risk of leukemia observed.

However, they did say the facility seems a plausible cause of the increased risk because the data showed significant associations between acute leukemia incidence and 3 surrogate measures of exposure—distance from the facility, prevailing winds, and simulated discharges of the radionuclide Ar-41.

An Van Nieuwenhuyse, MD, PhD, of the Scientific Institute of Public Health in Brussels, Belgium, and colleagues conducted this research and reported the results in the European Journal of Cancer Prevention.

Facilities

The study included 4 nuclear facilities in Belgium—Doel, Mol-Dessel, Fleurus, and Tihange. (The researchers also evaluated a fifth facility, Chooz, but they said it was not possible to draw conclusions regarding this site because the region around it is sparsely populated, which limits the number of cancer cases.)

Doel and Tihange are electricity-generating nuclear power plants that started up in 1975. The nuclear facility at Fleurus has produced radionuclides for medicine and industry since 1971.

The Mol-Dessel facility started up in 1956, and a combination of nuclear activities have taken place there, including scientific and technological research, applied research and metrology, operational waste management, the Belgian Underground Research Laboratory, and the production of fuel assemblies for pressurized-water reactors based on uranium oxide and mixed oxides.

Analysis

The researchers set out to determine whether there was an excess incidence of acute leukemia among children ages 0 to 14 who lived in the vicinity of the aforementioned nuclear facilities. The team analyzed data spanning the period from 2002 to 2008.

For all 4 facilities, the researchers used 2 different measures of surrogate exposure to radionuclide gaseous discharges—residential proximity to the nuclear site and prevailing wind directions.

For the Mol-Dessel site, the researchers also used estimated discharges of the radionuclide Ar-41 as a surrogate measure of exposure.

Results

The data did not show an increased incidence of acute leukemia among children living near the Doel, Tihange, or Fleurus facilities. However, children living within 15 km of the Mol-Dessel site had a significantly increased risk of acute leukemia.

In fact, the researchers said they observed statistically significant associations as a function of distance, prevailing winds, and simulated Ar-41 discharges, which suggests a potential link between acute leukemia incidence and the Mol-Dessel site.

The rate ratios for the Mol-Dessel facility, which were adjusted for age, sex, and socioeconomic status, were:

• 2.70 (95% CI: 1.15–6.33) for children living 0 to 5 km from the site (5 cases of acute leukemia)
• 1.82 (95% CI: 1.02–3.25) for children living 0 to 10 km from the site (11 cases of acute leukemia)
• 1.96 (95% CI: 1.19–3.22) for children living 0 to 15 km from the site (15 cases of acute leukemia)
• 1.09 (95% CI: 0.71–1.61) for children living 0 to 20 km from the site (21 cases of acute leukemia).

The 3 communities lying in the dominant wind direction of the Mol-Dessel nuclear site had rate ratios of 6.81 (95% CI: 2.28–20.32), 4.39 (95% CI: 1.46–13.17), and 3.74 (95% CI: 0.98–14.27).

The researchers calculated P values using Stone’s test, Bithell’s linear risk score test (LRS), and Bithell’s linear risk score test with corresponding ranks as a function of the different measures of surrogate exposure (LRS^r).

All 3 tests showed a significant association between acute leukemia incidence and proximity to the Mol-Dessel site (P<0.01 for all). However, only LRS and LRS^r showed a significant association for wind direction (P=0.01 and 0.03, respectively) and simulated radioactive discharges by Ar-41 (P<0.01 for both).

The researchers noted that, although these results suggest an association between acute childhood leukemia and the Mol-Dessel site, this study had limitations, and more research is needed.