Genetic testing

Credit: NIGMS

The time needed to sequence an entire human genome has decreased greatly in recent years, but analyzing the resulting 3 billion base pairs of genetic information from a single genome can take many months.

Now, researchers have found they can accelerate whole-genome analysis using a Cray XE6 supercomputer.

The team found this computer could process many genomes at once and was able to analyze 240 full genomes in a little over 2 days.

The researchers reported these results in Bioinformatics.

The team used Beagle, a Cray XE6 supercomputer located at Argonne National Laboratory in Illinois, in an attempt to analyze multiple genomes concurrently.

Using publicly available software packages and one quarter of its total capacity, the computer was able to align and call variants on 240 whole genomes in approximately 50 hours.

But the computer did not only speed up whole-genome analysis. It also increased the usable sequences per genome.

“Improving analysis through both speed and accuracy reduces the price per genome,” said study author Elizabeth McNally, MD, PhD, of the University of Chicago.

“With this approach, the price for analyzing an entire genome is less than the cost of looking at just a fraction of the genome. New technology promises to bring the costs of sequencing down to around $1000 per genome. Our goal is get the cost of analysis down into that range.”

The findings of this research have immediate medical applications, according to Dr McNally. She noted that she and her colleagues must often sequence genes from an initial patient as well as multiple family members in order to better understand and either treat or prevent a disease.

“We start genetic testing with the patient,” she said. “But when we find a significant mutation, we have to think about testing the whole family to identify individuals at risk.”

Furthermore, the range of testable mutations has greatly increased in recent years.

“In the early days, we would test 1 to 3 genes,” Dr McNally said. “In 2007, we did our first 5-gene panel. Now, we order 50 to 70 genes at a time, which usually gets us an answer. At that point, it can be more useful and less expensive to sequence the whole genome.”

The information from these genomes combined with careful attention to patient and family histories adds to our knowledge about inherited disorders, according to Dr McNally.

“It can refine the classification of these disorders,” she said. “By paying close attention to family members with genes that place them at increased risk, but who do not yet show signs of disease, we can investigate early phases of a disorder.”

Genetic testing

Credit: NIGMS

The time needed to sequence an entire human genome has decreased greatly in recent years, but analyzing the resulting 3 billion base pairs of genetic information from a single genome can take many months.

Now, researchers have found they can accelerate whole-genome analysis using a Cray XE6 supercomputer.

The team found this computer could process many genomes at once and was able to analyze 240 full genomes in a little over 2 days.

The researchers reported these results in Bioinformatics.

The team used Beagle, a Cray XE6 supercomputer located at Argonne National Laboratory in Illinois, in an attempt to analyze multiple genomes concurrently.

Using publicly available software packages and one quarter of its total capacity, the computer was able to align and call variants on 240 whole genomes in approximately 50 hours.

But the computer did not only speed up whole-genome analysis. It also increased the usable sequences per genome.

“Improving analysis through both speed and accuracy reduces the price per genome,” said study author Elizabeth McNally, MD, PhD, of the University of Chicago.

“With this approach, the price for analyzing an entire genome is less than the cost of looking at just a fraction of the genome. New technology promises to bring the costs of sequencing down to around $1000 per genome. Our goal is get the cost of analysis down into that range.”

The findings of this research have immediate medical applications, according to Dr McNally. She noted that she and her colleagues must often sequence genes from an initial patient as well as multiple family members in order to better understand and either treat or prevent a disease.

“We start genetic testing with the patient,” she said. “But when we find a significant mutation, we have to think about testing the whole family to identify individuals at risk.”

Furthermore, the range of testable mutations has greatly increased in recent years.

“In the early days, we would test 1 to 3 genes,” Dr McNally said. “In 2007, we did our first 5-gene panel. Now, we order 50 to 70 genes at a time, which usually gets us an answer. At that point, it can be more useful and less expensive to sequence the whole genome.”

The information from these genomes combined with careful attention to patient and family histories adds to our knowledge about inherited disorders, according to Dr McNally.

“It can refine the classification of these disorders,” she said. “By paying close attention to family members with genes that place them at increased risk, but who do not yet show signs of disease, we can investigate early phases of a disorder.”

Genetic testing

Credit: NIGMS

The time needed to sequence an entire human genome has decreased greatly in recent years, but analyzing the resulting 3 billion base pairs of genetic information from a single genome can take many months.

Now, researchers have found they can accelerate whole-genome analysis using a Cray XE6 supercomputer.

The team found this computer could process many genomes at once and was able to analyze 240 full genomes in a little over 2 days.

The researchers reported these results in Bioinformatics.

The team used Beagle, a Cray XE6 supercomputer located at Argonne National Laboratory in Illinois, in an attempt to analyze multiple genomes concurrently.

Using publicly available software packages and one quarter of its total capacity, the computer was able to align and call variants on 240 whole genomes in approximately 50 hours.

But the computer did not only speed up whole-genome analysis. It also increased the usable sequences per genome.

“Improving analysis through both speed and accuracy reduces the price per genome,” said study author Elizabeth McNally, MD, PhD, of the University of Chicago.

“With this approach, the price for analyzing an entire genome is less than the cost of looking at just a fraction of the genome. New technology promises to bring the costs of sequencing down to around $1000 per genome. Our goal is get the cost of analysis down into that range.”

The findings of this research have immediate medical applications, according to Dr McNally. She noted that she and her colleagues must often sequence genes from an initial patient as well as multiple family members in order to better understand and either treat or prevent a disease.

“We start genetic testing with the patient,” she said. “But when we find a significant mutation, we have to think about testing the whole family to identify individuals at risk.”

Furthermore, the range of testable mutations has greatly increased in recent years.

“In the early days, we would test 1 to 3 genes,” Dr McNally said. “In 2007, we did our first 5-gene panel. Now, we order 50 to 70 genes at a time, which usually gets us an answer. At that point, it can be more useful and less expensive to sequence the whole genome.”

The information from these genomes combined with careful attention to patient and family histories adds to our knowledge about inherited disorders, according to Dr McNally.

“It can refine the classification of these disorders,” she said. “By paying close attention to family members with genes that place them at increased risk, but who do not yet show signs of disease, we can investigate early phases of a disorder.”

Blood vessels

Two groups of researchers have shown that variants in the gene CECR1, which encodes for ADA2, are associated with blood vessel disorders.

One group found that mutations in CECR1 are associated with an ADA2 deficiency syndrome that is characterized by early onset, recurrent strokes and systemic vasculopathy.

The other group discovered that variants in CECR1 can cause polyarteritis nodosa vasculopathy.

Results of both studies appear in NEJM.

ADA2 deficiency syndrome

In the first study, Qing Zhou, PhD, of the National Human Genome Research Institute (NHGRI), and his colleagues used whole-exome sequencing to gain insight into the aforementioned syndrome, which was characterized by early onset lacunar strokes, systemic vasculopathy, and other symptoms.

The researchers performed whole-exome sequencing in 3 patients with the syndrome and their unaffected parents. In comparing 2 of the patients’ exomes to the exomes of their parents, the researchers located 2 variants in CECR1.

Sequencing a third patient revealed another harmful variant of CECR1, in addition to a small genomic deletion that shuts down the second copy of the gene.

The researchers needed only a sequence reading of that single gene to confirm that 3 other patients were affected by variants in CECR1. In all, these 6 patients were compound heterozygous for 8 mutations in CECR1.

The team discovered that these CECR1 mutations lead to the elimination of ADA2, which produces abnormalities and inflammation in blood vessel walls that ultimately result in the syndrome. So the team called the syndrome deficiency of ADA2 (DADA2).

To gain more insight into DADA2, the researchers induced ADA2 deficiency in a zebrafish model. They found that zebrafish embryos that produce less ADA2 than normal embryos have cerebral bleeds similar to those seen in some of the children with DADA2.

“Our study raises the possibility that the ADA2 pathway may contribute to susceptibility to stroke in the more general population,” said Daniel Kastner, MD, PhD, of NHGRI.

“This genome sequencing study expands what has previously been known about vascular biology. The role of ADA2 in such serious human disease is important and suggests that ADA2 variants may contribute to other, more common illnesses.”

Dr Kastner and his colleagues also sequenced the CECR1 gene in 3 patients from Turkey who had some of the symptoms of DADA2. These patients, who had polyarteritis nodosa (n=2) or small-vessel vasculitis (n=1), were homozygous for the p.Gly47Arg mutation.

ADA2 in polyarteritis nodosa

In the second study, researchers found the same mutation (p.Gly47Arg) in patients that emigrated to Israel from the country of Georgia.

“We now know that this mutation exists in the Middle East and in Pakistani populations and that it is not that uncommon,” said Ivona Aksentijevich, MD, of NHGRI. “This is the first time a single gene has been discovered that is involved in causing a system-wide form of vasculitis.”

To uncover this mutation, Paulina Navon-Elkan, MD, of the Shaare Zedek Medical Center in Jerusalem, and her colleagues sequenced 37 patients who had features of polyarteritis nodosa.

Nineteen patients were of Georgian Jewish ancestry. Sixteen of these patients came from 5 families, and 3 patients were unrelated. An additional 14 unrelated patients were of Turkish ancestry. And 4 German patients came from the same family.

The researchers found that, in all the families, vasculitis was a result of recessive mutations in CECR1.

All of the Georgian Jewish patients were homozygous for the p.Gly47Arg mutation. The German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations. And 1 Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations.

The researchers also analyzed serum specimens from the patients and found their ADA2 activity was significantly reduced.

Taking these results together, the team concluded that mutations in CECR1 cause loss of ADA2 function that can result in polyarteritis nodosa vasculopathy with a highly varied clinical expression.

Blood vessels

Two groups of researchers have shown that variants in the gene CECR1, which encodes for ADA2, are associated with blood vessel disorders.

One group found that mutations in CECR1 are associated with an ADA2 deficiency syndrome that is characterized by early onset, recurrent strokes and systemic vasculopathy.

The other group discovered that variants in CECR1 can cause polyarteritis nodosa vasculopathy.

Results of both studies appear in NEJM.

ADA2 deficiency syndrome

In the first study, Qing Zhou, PhD, of the National Human Genome Research Institute (NHGRI), and his colleagues used whole-exome sequencing to gain insight into the aforementioned syndrome, which was characterized by early onset lacunar strokes, systemic vasculopathy, and other symptoms.

The researchers performed whole-exome sequencing in 3 patients with the syndrome and their unaffected parents. In comparing 2 of the patients’ exomes to the exomes of their parents, the researchers located 2 variants in CECR1.

Sequencing a third patient revealed another harmful variant of CECR1, in addition to a small genomic deletion that shuts down the second copy of the gene.

The researchers needed only a sequence reading of that single gene to confirm that 3 other patients were affected by variants in CECR1. In all, these 6 patients were compound heterozygous for 8 mutations in CECR1.

The team discovered that these CECR1 mutations lead to the elimination of ADA2, which produces abnormalities and inflammation in blood vessel walls that ultimately result in the syndrome. So the team called the syndrome deficiency of ADA2 (DADA2).

To gain more insight into DADA2, the researchers induced ADA2 deficiency in a zebrafish model. They found that zebrafish embryos that produce less ADA2 than normal embryos have cerebral bleeds similar to those seen in some of the children with DADA2.

“Our study raises the possibility that the ADA2 pathway may contribute to susceptibility to stroke in the more general population,” said Daniel Kastner, MD, PhD, of NHGRI.

“This genome sequencing study expands what has previously been known about vascular biology. The role of ADA2 in such serious human disease is important and suggests that ADA2 variants may contribute to other, more common illnesses.”

Dr Kastner and his colleagues also sequenced the CECR1 gene in 3 patients from Turkey who had some of the symptoms of DADA2. These patients, who had polyarteritis nodosa (n=2) or small-vessel vasculitis (n=1), were homozygous for the p.Gly47Arg mutation.

ADA2 in polyarteritis nodosa

In the second study, researchers found the same mutation (p.Gly47Arg) in patients that emigrated to Israel from the country of Georgia.

“We now know that this mutation exists in the Middle East and in Pakistani populations and that it is not that uncommon,” said Ivona Aksentijevich, MD, of NHGRI. “This is the first time a single gene has been discovered that is involved in causing a system-wide form of vasculitis.”

To uncover this mutation, Paulina Navon-Elkan, MD, of the Shaare Zedek Medical Center in Jerusalem, and her colleagues sequenced 37 patients who had features of polyarteritis nodosa.

Nineteen patients were of Georgian Jewish ancestry. Sixteen of these patients came from 5 families, and 3 patients were unrelated. An additional 14 unrelated patients were of Turkish ancestry. And 4 German patients came from the same family.

The researchers found that, in all the families, vasculitis was a result of recessive mutations in CECR1.

All of the Georgian Jewish patients were homozygous for the p.Gly47Arg mutation. The German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations. And 1 Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations.

The researchers also analyzed serum specimens from the patients and found their ADA2 activity was significantly reduced.

Taking these results together, the team concluded that mutations in CECR1 cause loss of ADA2 function that can result in polyarteritis nodosa vasculopathy with a highly varied clinical expression.

Blood vessels

Two groups of researchers have shown that variants in the gene CECR1, which encodes for ADA2, are associated with blood vessel disorders.

One group found that mutations in CECR1 are associated with an ADA2 deficiency syndrome that is characterized by early onset, recurrent strokes and systemic vasculopathy.

The other group discovered that variants in CECR1 can cause polyarteritis nodosa vasculopathy.

Results of both studies appear in NEJM.

ADA2 deficiency syndrome

In the first study, Qing Zhou, PhD, of the National Human Genome Research Institute (NHGRI), and his colleagues used whole-exome sequencing to gain insight into the aforementioned syndrome, which was characterized by early onset lacunar strokes, systemic vasculopathy, and other symptoms.

The researchers performed whole-exome sequencing in 3 patients with the syndrome and their unaffected parents. In comparing 2 of the patients’ exomes to the exomes of their parents, the researchers located 2 variants in CECR1.

Sequencing a third patient revealed another harmful variant of CECR1, in addition to a small genomic deletion that shuts down the second copy of the gene.

The researchers needed only a sequence reading of that single gene to confirm that 3 other patients were affected by variants in CECR1. In all, these 6 patients were compound heterozygous for 8 mutations in CECR1.

The team discovered that these CECR1 mutations lead to the elimination of ADA2, which produces abnormalities and inflammation in blood vessel walls that ultimately result in the syndrome. So the team called the syndrome deficiency of ADA2 (DADA2).

To gain more insight into DADA2, the researchers induced ADA2 deficiency in a zebrafish model. They found that zebrafish embryos that produce less ADA2 than normal embryos have cerebral bleeds similar to those seen in some of the children with DADA2.

“Our study raises the possibility that the ADA2 pathway may contribute to susceptibility to stroke in the more general population,” said Daniel Kastner, MD, PhD, of NHGRI.

“This genome sequencing study expands what has previously been known about vascular biology. The role of ADA2 in such serious human disease is important and suggests that ADA2 variants may contribute to other, more common illnesses.”

Dr Kastner and his colleagues also sequenced the CECR1 gene in 3 patients from Turkey who had some of the symptoms of DADA2. These patients, who had polyarteritis nodosa (n=2) or small-vessel vasculitis (n=1), were homozygous for the p.Gly47Arg mutation.

ADA2 in polyarteritis nodosa

In the second study, researchers found the same mutation (p.Gly47Arg) in patients that emigrated to Israel from the country of Georgia.

“We now know that this mutation exists in the Middle East and in Pakistani populations and that it is not that uncommon,” said Ivona Aksentijevich, MD, of NHGRI. “This is the first time a single gene has been discovered that is involved in causing a system-wide form of vasculitis.”

To uncover this mutation, Paulina Navon-Elkan, MD, of the Shaare Zedek Medical Center in Jerusalem, and her colleagues sequenced 37 patients who had features of polyarteritis nodosa.

Nineteen patients were of Georgian Jewish ancestry. Sixteen of these patients came from 5 families, and 3 patients were unrelated. An additional 14 unrelated patients were of Turkish ancestry. And 4 German patients came from the same family.

The researchers found that, in all the families, vasculitis was a result of recessive mutations in CECR1.

All of the Georgian Jewish patients were homozygous for the p.Gly47Arg mutation. The German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations. And 1 Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations.

The researchers also analyzed serum specimens from the patients and found their ADA2 activity was significantly reduced.

Taking these results together, the team concluded that mutations in CECR1 cause loss of ADA2 function that can result in polyarteritis nodosa vasculopathy with a highly varied clinical expression.

While concepts and theories can go a long way, sometimes the best way to understand something is through a concrete example.

So, from time to time, ACO Insider will check in on a new accountable care organization composed of 14 independent physicians in 11 practices in McAllen, Tex.

We chose them because they share many of the same questions and concerns as quite a few of you readers: Will this work? Where do I begin? How can we do this, since we have no free time or money? How much will this cost? Will there be any shared savings? Do we have to affiliate with a hospital or a large practice? Are we too small? How do we apply for the Medicare Shared Savings Program (MSSP)? What will change in my practice?

The name of the ACO is Rio Grande Valley Health Alliance (RGVHA). It was formed in January 2012 as a "network-model" ACO, meaning that the physicians stay in their separate independent practices but participate in the ACO through contract. Its first – and as of this writing, only – ACO payer contract is with Medicare, the MSSP.

So far, there have been a number of unexpected highs and a number of unexpected lows. The primary care physicians of RGVHA hope that by sharing their story, they can help you better navigate your own ACO course.

Opportunity for primary care

Dr. Luis Delgado became intrigued by the possibility under accountable care of rewarding primary care physicians for the savings they generate while maintaining or improving quality. Instead of resisting change, he saw opportunity.

He also saw a chance to do something about McAllen’s reputation, gained through Dr. Atul Gawande’s 2009 article in the New Yorker entitled, "The Cost Conundrum." That article focused on McAllen’s Medicare health costs, which were almost twice those of its Rio Grande River neighbor, El Paso.

However, beyond having a vision, he had no know-how and no budget.

Fortunately, as readers of this column know, there is so much documented "low-hanging fruit" for primary care to generate savings through value-based care that the strategic time and expertise expenditures proved not to be significant. The legal structure and backroom business logistics for a small network-model primary care physician ACO are also relatively straightforward. RGVHA has two full-time administrative staffers, one part-time president (Dr. Delgado), and one part-time medical director (Dr. Roger Heredia).

However, the new ACO data collection, sorting, and reporting requirements were somewhat daunting – that is, until they met Dr. Gretchen Hoyle of MD Online Solutions (MDOS). Dr. Hoyle is a practicing pediatrician who spearheaded the design of a physician-friendly care management data system for her practice and found it ideal for the accountable care era. Her company targets small- to medium-sized physician-led ACOs.

MDOS was able to tailor a nimble ACO solution scaled to RGVHA’s needs, thus allowing RGVHA to supply its last missing piece in a cost-effective manner. Because she is a practicing physician, Dr. Hoyle helps interpret the data and leads a weekly data-driven staff conference call with the ACO’s nurse care coordinators.

Approved for the Medicare ACO

Despite initial fears, RGVHA found that the MSSP application process was not intimidating at all. It turned out to be a reflection of its business structure and primary care physician ACO strategy.

"If you get your game plan together ahead of time, independent primary care physicians should be successful in applying for the Medicare Shared Savings Program," stated Dr. Delgado. "We found that Medicare is supportive of this type of ACO, I guess because it sees their potential to improve health care," he said.

The Centers for Medicare & Medicaid Services does indeed support these types of ACOs, as RGVHA qualified for one of the last Advanced Payment Program grants. The CMS is so confident that these physician-led, nonmetropolitan ACOs will work, that the agency actually fronted the infrastructure and operational money to them. RGVHA was one of the last grantees of this one-time appropriation.

They began the MSSP program Jan. 1, 2013, opting not to take risk and to receive 50% of the savings they generated for the 5,000 patients attributed to them, if quality and patient satisfaction metrics are met.

‘I haven’t had this much fun practicing medicine in 10 years!’

To decide what type of initiatives to undertake, the physicians read the Physician’s Accountable Care Toolkit (profiled in an earlier column) and convened a weekend workshop. They were pleasantly surprised when they realized that so many savings and quality improvement opportunities are available to primary care physicians under accountable care – and control over the physician-patient relationship was being returned to them.

They targeted diabetes management, patient engagement, best practices for enhanced prevention and wellness, and home health management.

One physician summed up the mood when she exclaimed, "I haven’t had this much fun practicing medicine in 10 years."

As they celebrate their first year under the MSSP, how are they doing? Check in next month for part 2: Our secret weapon, and our biggest disappointment.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians in forming integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or at 919-821-6612.

While concepts and theories can go a long way, sometimes the best way to understand something is through a concrete example.

So, from time to time, ACO Insider will check in on a new accountable care organization composed of 14 independent physicians in 11 practices in McAllen, Tex.

We chose them because they share many of the same questions and concerns as quite a few of you readers: Will this work? Where do I begin? How can we do this, since we have no free time or money? How much will this cost? Will there be any shared savings? Do we have to affiliate with a hospital or a large practice? Are we too small? How do we apply for the Medicare Shared Savings Program (MSSP)? What will change in my practice?

The name of the ACO is Rio Grande Valley Health Alliance (RGVHA). It was formed in January 2012 as a "network-model" ACO, meaning that the physicians stay in their separate independent practices but participate in the ACO through contract. Its first – and as of this writing, only – ACO payer contract is with Medicare, the MSSP.

So far, there have been a number of unexpected highs and a number of unexpected lows. The primary care physicians of RGVHA hope that by sharing their story, they can help you better navigate your own ACO course.

Opportunity for primary care

Dr. Luis Delgado became intrigued by the possibility under accountable care of rewarding primary care physicians for the savings they generate while maintaining or improving quality. Instead of resisting change, he saw opportunity.

He also saw a chance to do something about McAllen’s reputation, gained through Dr. Atul Gawande’s 2009 article in the New Yorker entitled, "The Cost Conundrum." That article focused on McAllen’s Medicare health costs, which were almost twice those of its Rio Grande River neighbor, El Paso.

However, beyond having a vision, he had no know-how and no budget.

Fortunately, as readers of this column know, there is so much documented "low-hanging fruit" for primary care to generate savings through value-based care that the strategic time and expertise expenditures proved not to be significant. The legal structure and backroom business logistics for a small network-model primary care physician ACO are also relatively straightforward. RGVHA has two full-time administrative staffers, one part-time president (Dr. Delgado), and one part-time medical director (Dr. Roger Heredia).

However, the new ACO data collection, sorting, and reporting requirements were somewhat daunting – that is, until they met Dr. Gretchen Hoyle of MD Online Solutions (MDOS). Dr. Hoyle is a practicing pediatrician who spearheaded the design of a physician-friendly care management data system for her practice and found it ideal for the accountable care era. Her company targets small- to medium-sized physician-led ACOs.

MDOS was able to tailor a nimble ACO solution scaled to RGVHA’s needs, thus allowing RGVHA to supply its last missing piece in a cost-effective manner. Because she is a practicing physician, Dr. Hoyle helps interpret the data and leads a weekly data-driven staff conference call with the ACO’s nurse care coordinators.

Approved for the Medicare ACO

Despite initial fears, RGVHA found that the MSSP application process was not intimidating at all. It turned out to be a reflection of its business structure and primary care physician ACO strategy.

"If you get your game plan together ahead of time, independent primary care physicians should be successful in applying for the Medicare Shared Savings Program," stated Dr. Delgado. "We found that Medicare is supportive of this type of ACO, I guess because it sees their potential to improve health care," he said.

The Centers for Medicare & Medicaid Services does indeed support these types of ACOs, as RGVHA qualified for one of the last Advanced Payment Program grants. The CMS is so confident that these physician-led, nonmetropolitan ACOs will work, that the agency actually fronted the infrastructure and operational money to them. RGVHA was one of the last grantees of this one-time appropriation.

They began the MSSP program Jan. 1, 2013, opting not to take risk and to receive 50% of the savings they generated for the 5,000 patients attributed to them, if quality and patient satisfaction metrics are met.

‘I haven’t had this much fun practicing medicine in 10 years!’

To decide what type of initiatives to undertake, the physicians read the Physician’s Accountable Care Toolkit (profiled in an earlier column) and convened a weekend workshop. They were pleasantly surprised when they realized that so many savings and quality improvement opportunities are available to primary care physicians under accountable care – and control over the physician-patient relationship was being returned to them.

They targeted diabetes management, patient engagement, best practices for enhanced prevention and wellness, and home health management.

One physician summed up the mood when she exclaimed, "I haven’t had this much fun practicing medicine in 10 years."

As they celebrate their first year under the MSSP, how are they doing? Check in next month for part 2: Our secret weapon, and our biggest disappointment.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians in forming integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or at 919-821-6612.

While concepts and theories can go a long way, sometimes the best way to understand something is through a concrete example.

So, from time to time, ACO Insider will check in on a new accountable care organization composed of 14 independent physicians in 11 practices in McAllen, Tex.

We chose them because they share many of the same questions and concerns as quite a few of you readers: Will this work? Where do I begin? How can we do this, since we have no free time or money? How much will this cost? Will there be any shared savings? Do we have to affiliate with a hospital or a large practice? Are we too small? How do we apply for the Medicare Shared Savings Program (MSSP)? What will change in my practice?

The name of the ACO is Rio Grande Valley Health Alliance (RGVHA). It was formed in January 2012 as a "network-model" ACO, meaning that the physicians stay in their separate independent practices but participate in the ACO through contract. Its first – and as of this writing, only – ACO payer contract is with Medicare, the MSSP.

So far, there have been a number of unexpected highs and a number of unexpected lows. The primary care physicians of RGVHA hope that by sharing their story, they can help you better navigate your own ACO course.

Opportunity for primary care

Dr. Luis Delgado became intrigued by the possibility under accountable care of rewarding primary care physicians for the savings they generate while maintaining or improving quality. Instead of resisting change, he saw opportunity.

He also saw a chance to do something about McAllen’s reputation, gained through Dr. Atul Gawande’s 2009 article in the New Yorker entitled, "The Cost Conundrum." That article focused on McAllen’s Medicare health costs, which were almost twice those of its Rio Grande River neighbor, El Paso.

However, beyond having a vision, he had no know-how and no budget.

Fortunately, as readers of this column know, there is so much documented "low-hanging fruit" for primary care to generate savings through value-based care that the strategic time and expertise expenditures proved not to be significant. The legal structure and backroom business logistics for a small network-model primary care physician ACO are also relatively straightforward. RGVHA has two full-time administrative staffers, one part-time president (Dr. Delgado), and one part-time medical director (Dr. Roger Heredia).

However, the new ACO data collection, sorting, and reporting requirements were somewhat daunting – that is, until they met Dr. Gretchen Hoyle of MD Online Solutions (MDOS). Dr. Hoyle is a practicing pediatrician who spearheaded the design of a physician-friendly care management data system for her practice and found it ideal for the accountable care era. Her company targets small- to medium-sized physician-led ACOs.

MDOS was able to tailor a nimble ACO solution scaled to RGVHA’s needs, thus allowing RGVHA to supply its last missing piece in a cost-effective manner. Because she is a practicing physician, Dr. Hoyle helps interpret the data and leads a weekly data-driven staff conference call with the ACO’s nurse care coordinators.

Approved for the Medicare ACO

Despite initial fears, RGVHA found that the MSSP application process was not intimidating at all. It turned out to be a reflection of its business structure and primary care physician ACO strategy.

"If you get your game plan together ahead of time, independent primary care physicians should be successful in applying for the Medicare Shared Savings Program," stated Dr. Delgado. "We found that Medicare is supportive of this type of ACO, I guess because it sees their potential to improve health care," he said.

The Centers for Medicare & Medicaid Services does indeed support these types of ACOs, as RGVHA qualified for one of the last Advanced Payment Program grants. The CMS is so confident that these physician-led, nonmetropolitan ACOs will work, that the agency actually fronted the infrastructure and operational money to them. RGVHA was one of the last grantees of this one-time appropriation.

They began the MSSP program Jan. 1, 2013, opting not to take risk and to receive 50% of the savings they generated for the 5,000 patients attributed to them, if quality and patient satisfaction metrics are met.

‘I haven’t had this much fun practicing medicine in 10 years!’

To decide what type of initiatives to undertake, the physicians read the Physician’s Accountable Care Toolkit (profiled in an earlier column) and convened a weekend workshop. They were pleasantly surprised when they realized that so many savings and quality improvement opportunities are available to primary care physicians under accountable care – and control over the physician-patient relationship was being returned to them.

They targeted diabetes management, patient engagement, best practices for enhanced prevention and wellness, and home health management.

One physician summed up the mood when she exclaimed, "I haven’t had this much fun practicing medicine in 10 years."

As they celebrate their first year under the MSSP, how are they doing? Check in next month for part 2: Our secret weapon, and our biggest disappointment.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians in forming integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or at 919-821-6612.

In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

[email protected]

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”