Hospitalist Jordan Messler, MD, SFHM, has experienced SHM’s mentored-implementation program as both mentee and mentor. So when he heard that the mentored-implementation model was named the winner of the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level Award, he knew it was well-earned.

Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award. We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.

—Joseph Ming-Wah Li, MD, SFHM, SHM president

“The biggest aspect of these programs has been the collegiality and the learning from others,” says Dr. Messler, medical director at Morton Plant Hospital in Clearwater, Fla. “That’s really the core of this. We’ve all felt that we’re out on an island and we’re all building these projects from the ground up. We all probably at one point in a meeting say, ‘Someone else must have solved this.’ ... These mentored-implementation programs say, ‘Yes, of course other folks have solved this.’” 

SHM is the first professional society to earn the award, bestowed by the National Quality Forum (NQF) and The Joint Commission. The model has helped propel SHM’s Glycemic Control Mentored Implementation (GCMI) Program, Project BOOST (Better Outcomes for Older Adults through Safe Transitions), and the VTE Prevention Collaborative.

Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to an announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM president Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort.”

NQF president and chief executive Janet Corrigan, PhD, MBA, says that one of the hallmarks of SHM’s program is its ability to be applied to different quality initiatives. Corrigan adds that while a professional society had never previously won the national award, SHM’s execution in creating, implementing, and providing follow-up resources helped differentiate the construct.

“We want to shed light on the kinds of things that are working and encourage others to emulate them, to build on them, and to reinvent them in new and even better ways,” Corrigan says. “It is a whole process of quality improvement.”

Dr. Li says the honor is a milestone for SHM, but the society must not rest on its laurels because it “hit a home run.” Instead, the society should use the momentum of the award to push for and apply for more QI programs. The more successful programs the society and its members launch and successfully implement, the more HM as a field will be considered a leader in quality improvement, he adds.

“We’re an absolute infant compared to many other medical organizations and other medical societies,” Dr. Li says. “Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award.

"We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.”

 Richard Quinn is a freelance writer based in New Jersey. 

Hospitalist Jordan Messler, MD, SFHM, has experienced SHM’s mentored-implementation program as both mentee and mentor. So when he heard that the mentored-implementation model was named the winner of the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level Award, he knew it was well-earned.

Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award. We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.

—Joseph Ming-Wah Li, MD, SFHM, SHM president

“The biggest aspect of these programs has been the collegiality and the learning from others,” says Dr. Messler, medical director at Morton Plant Hospital in Clearwater, Fla. “That’s really the core of this. We’ve all felt that we’re out on an island and we’re all building these projects from the ground up. We all probably at one point in a meeting say, ‘Someone else must have solved this.’ ... These mentored-implementation programs say, ‘Yes, of course other folks have solved this.’” 

SHM is the first professional society to earn the award, bestowed by the National Quality Forum (NQF) and The Joint Commission. The model has helped propel SHM’s Glycemic Control Mentored Implementation (GCMI) Program, Project BOOST (Better Outcomes for Older Adults through Safe Transitions), and the VTE Prevention Collaborative.

Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to an announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM president Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort.”

NQF president and chief executive Janet Corrigan, PhD, MBA, says that one of the hallmarks of SHM’s program is its ability to be applied to different quality initiatives. Corrigan adds that while a professional society had never previously won the national award, SHM’s execution in creating, implementing, and providing follow-up resources helped differentiate the construct.

“We want to shed light on the kinds of things that are working and encourage others to emulate them, to build on them, and to reinvent them in new and even better ways,” Corrigan says. “It is a whole process of quality improvement.”

Dr. Li says the honor is a milestone for SHM, but the society must not rest on its laurels because it “hit a home run.” Instead, the society should use the momentum of the award to push for and apply for more QI programs. The more successful programs the society and its members launch and successfully implement, the more HM as a field will be considered a leader in quality improvement, he adds.

“We’re an absolute infant compared to many other medical organizations and other medical societies,” Dr. Li says. “Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award.

"We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.”

 Richard Quinn is a freelance writer based in New Jersey. 

Hospitalist Jordan Messler, MD, SFHM, has experienced SHM’s mentored-implementation program as both mentee and mentor. So when he heard that the mentored-implementation model was named the winner of the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level Award, he knew it was well-earned.

Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award. We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.

—Joseph Ming-Wah Li, MD, SFHM, SHM president

“The biggest aspect of these programs has been the collegiality and the learning from others,” says Dr. Messler, medical director at Morton Plant Hospital in Clearwater, Fla. “That’s really the core of this. We’ve all felt that we’re out on an island and we’re all building these projects from the ground up. We all probably at one point in a meeting say, ‘Someone else must have solved this.’ ... These mentored-implementation programs say, ‘Yes, of course other folks have solved this.’” 

SHM is the first professional society to earn the award, bestowed by the National Quality Forum (NQF) and The Joint Commission. The model has helped propel SHM’s Glycemic Control Mentored Implementation (GCMI) Program, Project BOOST (Better Outcomes for Older Adults through Safe Transitions), and the VTE Prevention Collaborative.

Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to an announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM president Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort.”

NQF president and chief executive Janet Corrigan, PhD, MBA, says that one of the hallmarks of SHM’s program is its ability to be applied to different quality initiatives. Corrigan adds that while a professional society had never previously won the national award, SHM’s execution in creating, implementing, and providing follow-up resources helped differentiate the construct.

“We want to shed light on the kinds of things that are working and encourage others to emulate them, to build on them, and to reinvent them in new and even better ways,” Corrigan says. “It is a whole process of quality improvement.”

Dr. Li says the honor is a milestone for SHM, but the society must not rest on its laurels because it “hit a home run.” Instead, the society should use the momentum of the award to push for and apply for more QI programs. The more successful programs the society and its members launch and successfully implement, the more HM as a field will be considered a leader in quality improvement, he adds.

“We’re an absolute infant compared to many other medical organizations and other medical societies,” Dr. Li says. “Hospitalists and SHM should be very proud that NQF and The Joint Commission chose to bestow this award onto SHM. But at the end of the day, we at SHM also recognize that this is an award.

"We’re going to celebrate in San Diego with everybody, but once the [annual] meeting is over, we’re going to roll up our sleeves. There’s a heck of a lot more work to get done.”

 Richard Quinn is a freelance writer based in New Jersey. 

More detailed genetic profiling of patients with acute myeloid leukemia and of those with precursor myelodysplastic syndromes is likely to improve prognostic and therapeutic decision making, according to two separate studies published online March 14 in the New England Journal of Medicine.

In one study, investigators found that the presence of DNMT3A and NPM1 mutations and MLL translocations predicted an improved outcome when patients received high-dose daunorubicin instead of the standard dose in induction chemotherapy for acute myeloid leukemia (AML).

The results suggest that "mutational profiling can be used to determine which patients will benefit from dose-intensive induction therapy," wrote Jay P. Patel of the human oncology and pathogenesis program at Memorial Sloan-Kettering Cancer Center, New York, and his associates.

In the other study, researchers reported that "nearly all" of the bone marrow cells were clonally derived in paired samples of skin and bone marrow from seven patients with myelodysplastic syndromes (MDS) and secondary AML. Founding clones and daughter subclones in all seven paired samples had recurrent gene mutations, including at least one mutation in a coding gene.

"Although clonality is not sufficient to define malignant transformation, it is a cardinal manifestation of most human cancers, and our findings suggest that the myelodysplastic syndromes and secondary AML are both highly clonal hematologic cancers," said Dr. Matthew J. Walter of the departments of internal medicine and genetics at the Siteman Cancer Center, Washington University, St. Louis, and his associates.

Mutational Analysis of Trial Results

In the first study, researchers performed a more-extensive mutational analysis than is typically done to better discriminate among patients with different prognoses.

"Previous studies have suggested that mutational analysis of [the genes] CEBPA, NPM1, and FLT3-ITD can be used to stratify risk among patients with intermediate-risk AML," wrote Mr. Patel and his colleagues.

"We hypothesized that integrated mutational analysis of all known molecular alterations occurring in more than 5% of patients with AML would allow us to identify novel molecular markers of outcome ... and to identify molecularly defined subgroups of patients who would benefit from dose-intensified induction therapy."

For DNA extraction and profiling, the investigators used diagnostic samples of bone marrow and peripheral blood from 398 patients who were participating in the phase III ECOG (Eastern Cooperative Oncology Group) E1900 clinical trial in which two doses of induction therapy were tested. They found that 97.3% of the study subjects had mutations in 18 genes, and performed extensive mutational analysis of these 18 candidate genes.

The results led them to identify three distinct risk groups. Patients with favorable genetic profiles had a 3-year overall survival of 64% and had not yet reached a median survival; those with intermediate-risk genetic profiles had a 3-year survival of 42% and a median survival of 25 months; and those with unfavorable genetic profiles had a 3-year overall survival of 12% and a median survival of 10 months.

These findings were then validated in a separate group of 104 patients from the same clinical trial. The value of the genetic risk profiles was confirmed, with the favorable, intermediate, and unfavorable profiles accurately predicting patient outcomes independently of patient age, white cell count, induction dose, transplantation status, and type of postremission therapy, Mr. Patel and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1112304]).

Moreover, the 3-year overall survival rate in patients with a mutation in the DNMT3A or NPM1 genes or a MLL translocation was 44% with high-dose chemotherapy vs. 25% with the standard dose. In patients with other genotypes, it was 35% with the high-dose regimen and 39% with the standard dose.

"These data indicate that more detailed genetic analysis may lead to improved risk stratification and identification of patients who can benefit from more intensive induction chemotherapy. The challenge is to provide genetic information in a timely and affordable way and show that this information could prospectively influence treatment decisions," they noted.

Founding MDS Clones Persist in AML

In the second study, Dr. Walter and his associates used bone marrow biopsy specimens from seven patients who progressed from MDS to AML to define changes in the proportion of clonal cells and the genetic architecture that took place during that progression.

Several genes have already been identified that show recurrent mutations during this process, "but our understanding of the total number and clonal distribution of mutations in this disease is limited," they noted.

For each subject, DNA sequences were obtained from samples of normal skin, bone marrow obtained during the MDS stage, and bone marrow obtained during the secondary AML stage, to analyze mutations. In all seven samples, the founding clones (containing 182-660 mutations) persisted in the secondary samples, while acquiring at least one new mutation predicting translational consequences.

"We have found that the proportion of neoplastic bone marrow cells is indistinguishable [between] myelodysplastic-syndrome and secondary-AML samples, suggesting that the myelodysplastic syndromes are as clonal as secondary AML," Dr. Walter and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1106968]).

There are three major clinical implications, according to the authors.

First, MDS is currently distinguished from secondary AML based on hand counting of bone marrow myeloblasts – a method prone to inaccuracy but nonetheless relied upon to drive major treatment decisions. "Ultimately, identifying the patterns of pathogenic mutations and their clonality in bone marrow samples ... should lead to greater diagnostic certainty and improved prognostic algorithms," the investigators said.

Second, the dominant AML clone was derived from a founding MDS clone in every case, suggesting that "therapies targeted to these early mutations might be the most effective strategy for eliminating disease-propagating cells and improving the rate of response to traditional chemotherapy."

Third, it is possible that progression from MDS to AML "is driven not only by the presence of recurrent mutations ... but also by the clone ([that is], founding vs. daughter) in which they arise." Combining genotyping of samples with analysis of the clonal architecture "may yield more informative biomarkers and a better understanding of the pathogenesis of the myelodysplastic syndrome," Dr. Walter and his associates said.

Dr. Patel’s study was supported by the National Cancer Institute Physical Sciences Oncology Center, Gabrielle’s Angel Fund, the Starr Cancer Consortium, the Peter Solomon Fund, the American Society of Hematology, the Leukemia and Lymphoma Society, the Fund for Scientific Research Flanders, Burroughs Wellcome, the Sackler Center for Biomedical and Research Sciences, and the Howard Hughes Medical Institute. One of Dr. Patel’s associates reported ties to Agios, Incyte, and Novartis. Dr. Walter’s study was supported by the National Institutes of Health, the Howard Hughes Medical Institute, and the National Center for Research Resources. He and his associates reported no financial conflicts of interest.

More detailed genetic profiling of patients with acute myeloid leukemia and of those with precursor myelodysplastic syndromes is likely to improve prognostic and therapeutic decision making, according to two separate studies published online March 14 in the New England Journal of Medicine.

In one study, investigators found that the presence of DNMT3A and NPM1 mutations and MLL translocations predicted an improved outcome when patients received high-dose daunorubicin instead of the standard dose in induction chemotherapy for acute myeloid leukemia (AML).

The results suggest that "mutational profiling can be used to determine which patients will benefit from dose-intensive induction therapy," wrote Jay P. Patel of the human oncology and pathogenesis program at Memorial Sloan-Kettering Cancer Center, New York, and his associates.

In the other study, researchers reported that "nearly all" of the bone marrow cells were clonally derived in paired samples of skin and bone marrow from seven patients with myelodysplastic syndromes (MDS) and secondary AML. Founding clones and daughter subclones in all seven paired samples had recurrent gene mutations, including at least one mutation in a coding gene.

"Although clonality is not sufficient to define malignant transformation, it is a cardinal manifestation of most human cancers, and our findings suggest that the myelodysplastic syndromes and secondary AML are both highly clonal hematologic cancers," said Dr. Matthew J. Walter of the departments of internal medicine and genetics at the Siteman Cancer Center, Washington University, St. Louis, and his associates.

Mutational Analysis of Trial Results

In the first study, researchers performed a more-extensive mutational analysis than is typically done to better discriminate among patients with different prognoses.

"Previous studies have suggested that mutational analysis of [the genes] CEBPA, NPM1, and FLT3-ITD can be used to stratify risk among patients with intermediate-risk AML," wrote Mr. Patel and his colleagues.

"We hypothesized that integrated mutational analysis of all known molecular alterations occurring in more than 5% of patients with AML would allow us to identify novel molecular markers of outcome ... and to identify molecularly defined subgroups of patients who would benefit from dose-intensified induction therapy."

For DNA extraction and profiling, the investigators used diagnostic samples of bone marrow and peripheral blood from 398 patients who were participating in the phase III ECOG (Eastern Cooperative Oncology Group) E1900 clinical trial in which two doses of induction therapy were tested. They found that 97.3% of the study subjects had mutations in 18 genes, and performed extensive mutational analysis of these 18 candidate genes.

The results led them to identify three distinct risk groups. Patients with favorable genetic profiles had a 3-year overall survival of 64% and had not yet reached a median survival; those with intermediate-risk genetic profiles had a 3-year survival of 42% and a median survival of 25 months; and those with unfavorable genetic profiles had a 3-year overall survival of 12% and a median survival of 10 months.

These findings were then validated in a separate group of 104 patients from the same clinical trial. The value of the genetic risk profiles was confirmed, with the favorable, intermediate, and unfavorable profiles accurately predicting patient outcomes independently of patient age, white cell count, induction dose, transplantation status, and type of postremission therapy, Mr. Patel and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1112304]).

Moreover, the 3-year overall survival rate in patients with a mutation in the DNMT3A or NPM1 genes or a MLL translocation was 44% with high-dose chemotherapy vs. 25% with the standard dose. In patients with other genotypes, it was 35% with the high-dose regimen and 39% with the standard dose.

"These data indicate that more detailed genetic analysis may lead to improved risk stratification and identification of patients who can benefit from more intensive induction chemotherapy. The challenge is to provide genetic information in a timely and affordable way and show that this information could prospectively influence treatment decisions," they noted.

Founding MDS Clones Persist in AML

In the second study, Dr. Walter and his associates used bone marrow biopsy specimens from seven patients who progressed from MDS to AML to define changes in the proportion of clonal cells and the genetic architecture that took place during that progression.

Several genes have already been identified that show recurrent mutations during this process, "but our understanding of the total number and clonal distribution of mutations in this disease is limited," they noted.

For each subject, DNA sequences were obtained from samples of normal skin, bone marrow obtained during the MDS stage, and bone marrow obtained during the secondary AML stage, to analyze mutations. In all seven samples, the founding clones (containing 182-660 mutations) persisted in the secondary samples, while acquiring at least one new mutation predicting translational consequences.

"We have found that the proportion of neoplastic bone marrow cells is indistinguishable [between] myelodysplastic-syndrome and secondary-AML samples, suggesting that the myelodysplastic syndromes are as clonal as secondary AML," Dr. Walter and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1106968]).

There are three major clinical implications, according to the authors.

First, MDS is currently distinguished from secondary AML based on hand counting of bone marrow myeloblasts – a method prone to inaccuracy but nonetheless relied upon to drive major treatment decisions. "Ultimately, identifying the patterns of pathogenic mutations and their clonality in bone marrow samples ... should lead to greater diagnostic certainty and improved prognostic algorithms," the investigators said.

Second, the dominant AML clone was derived from a founding MDS clone in every case, suggesting that "therapies targeted to these early mutations might be the most effective strategy for eliminating disease-propagating cells and improving the rate of response to traditional chemotherapy."

Third, it is possible that progression from MDS to AML "is driven not only by the presence of recurrent mutations ... but also by the clone ([that is], founding vs. daughter) in which they arise." Combining genotyping of samples with analysis of the clonal architecture "may yield more informative biomarkers and a better understanding of the pathogenesis of the myelodysplastic syndrome," Dr. Walter and his associates said.

Dr. Patel’s study was supported by the National Cancer Institute Physical Sciences Oncology Center, Gabrielle’s Angel Fund, the Starr Cancer Consortium, the Peter Solomon Fund, the American Society of Hematology, the Leukemia and Lymphoma Society, the Fund for Scientific Research Flanders, Burroughs Wellcome, the Sackler Center for Biomedical and Research Sciences, and the Howard Hughes Medical Institute. One of Dr. Patel’s associates reported ties to Agios, Incyte, and Novartis. Dr. Walter’s study was supported by the National Institutes of Health, the Howard Hughes Medical Institute, and the National Center for Research Resources. He and his associates reported no financial conflicts of interest.

More detailed genetic profiling of patients with acute myeloid leukemia and of those with precursor myelodysplastic syndromes is likely to improve prognostic and therapeutic decision making, according to two separate studies published online March 14 in the New England Journal of Medicine.

In one study, investigators found that the presence of DNMT3A and NPM1 mutations and MLL translocations predicted an improved outcome when patients received high-dose daunorubicin instead of the standard dose in induction chemotherapy for acute myeloid leukemia (AML).

The results suggest that "mutational profiling can be used to determine which patients will benefit from dose-intensive induction therapy," wrote Jay P. Patel of the human oncology and pathogenesis program at Memorial Sloan-Kettering Cancer Center, New York, and his associates.

In the other study, researchers reported that "nearly all" of the bone marrow cells were clonally derived in paired samples of skin and bone marrow from seven patients with myelodysplastic syndromes (MDS) and secondary AML. Founding clones and daughter subclones in all seven paired samples had recurrent gene mutations, including at least one mutation in a coding gene.

"Although clonality is not sufficient to define malignant transformation, it is a cardinal manifestation of most human cancers, and our findings suggest that the myelodysplastic syndromes and secondary AML are both highly clonal hematologic cancers," said Dr. Matthew J. Walter of the departments of internal medicine and genetics at the Siteman Cancer Center, Washington University, St. Louis, and his associates.

Mutational Analysis of Trial Results

In the first study, researchers performed a more-extensive mutational analysis than is typically done to better discriminate among patients with different prognoses.

"Previous studies have suggested that mutational analysis of [the genes] CEBPA, NPM1, and FLT3-ITD can be used to stratify risk among patients with intermediate-risk AML," wrote Mr. Patel and his colleagues.

"We hypothesized that integrated mutational analysis of all known molecular alterations occurring in more than 5% of patients with AML would allow us to identify novel molecular markers of outcome ... and to identify molecularly defined subgroups of patients who would benefit from dose-intensified induction therapy."

For DNA extraction and profiling, the investigators used diagnostic samples of bone marrow and peripheral blood from 398 patients who were participating in the phase III ECOG (Eastern Cooperative Oncology Group) E1900 clinical trial in which two doses of induction therapy were tested. They found that 97.3% of the study subjects had mutations in 18 genes, and performed extensive mutational analysis of these 18 candidate genes.

The results led them to identify three distinct risk groups. Patients with favorable genetic profiles had a 3-year overall survival of 64% and had not yet reached a median survival; those with intermediate-risk genetic profiles had a 3-year survival of 42% and a median survival of 25 months; and those with unfavorable genetic profiles had a 3-year overall survival of 12% and a median survival of 10 months.

These findings were then validated in a separate group of 104 patients from the same clinical trial. The value of the genetic risk profiles was confirmed, with the favorable, intermediate, and unfavorable profiles accurately predicting patient outcomes independently of patient age, white cell count, induction dose, transplantation status, and type of postremission therapy, Mr. Patel and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1112304]).

Moreover, the 3-year overall survival rate in patients with a mutation in the DNMT3A or NPM1 genes or a MLL translocation was 44% with high-dose chemotherapy vs. 25% with the standard dose. In patients with other genotypes, it was 35% with the high-dose regimen and 39% with the standard dose.

"These data indicate that more detailed genetic analysis may lead to improved risk stratification and identification of patients who can benefit from more intensive induction chemotherapy. The challenge is to provide genetic information in a timely and affordable way and show that this information could prospectively influence treatment decisions," they noted.

Founding MDS Clones Persist in AML

In the second study, Dr. Walter and his associates used bone marrow biopsy specimens from seven patients who progressed from MDS to AML to define changes in the proportion of clonal cells and the genetic architecture that took place during that progression.

Several genes have already been identified that show recurrent mutations during this process, "but our understanding of the total number and clonal distribution of mutations in this disease is limited," they noted.

For each subject, DNA sequences were obtained from samples of normal skin, bone marrow obtained during the MDS stage, and bone marrow obtained during the secondary AML stage, to analyze mutations. In all seven samples, the founding clones (containing 182-660 mutations) persisted in the secondary samples, while acquiring at least one new mutation predicting translational consequences.

"We have found that the proportion of neoplastic bone marrow cells is indistinguishable [between] myelodysplastic-syndrome and secondary-AML samples, suggesting that the myelodysplastic syndromes are as clonal as secondary AML," Dr. Walter and his colleagues said (N. Engl. J. Med. 2012 March 14 [doi:10.1056/NEJMoa1106968]).

There are three major clinical implications, according to the authors.

First, MDS is currently distinguished from secondary AML based on hand counting of bone marrow myeloblasts – a method prone to inaccuracy but nonetheless relied upon to drive major treatment decisions. "Ultimately, identifying the patterns of pathogenic mutations and their clonality in bone marrow samples ... should lead to greater diagnostic certainty and improved prognostic algorithms," the investigators said.

Second, the dominant AML clone was derived from a founding MDS clone in every case, suggesting that "therapies targeted to these early mutations might be the most effective strategy for eliminating disease-propagating cells and improving the rate of response to traditional chemotherapy."

Third, it is possible that progression from MDS to AML "is driven not only by the presence of recurrent mutations ... but also by the clone ([that is], founding vs. daughter) in which they arise." Combining genotyping of samples with analysis of the clonal architecture "may yield more informative biomarkers and a better understanding of the pathogenesis of the myelodysplastic syndrome," Dr. Walter and his associates said.

Dr. Patel’s study was supported by the National Cancer Institute Physical Sciences Oncology Center, Gabrielle’s Angel Fund, the Starr Cancer Consortium, the Peter Solomon Fund, the American Society of Hematology, the Leukemia and Lymphoma Society, the Fund for Scientific Research Flanders, Burroughs Wellcome, the Sackler Center for Biomedical and Research Sciences, and the Howard Hughes Medical Institute. One of Dr. Patel’s associates reported ties to Agios, Incyte, and Novartis. Dr. Walter’s study was supported by the National Institutes of Health, the Howard Hughes Medical Institute, and the National Center for Research Resources. He and his associates reported no financial conflicts of interest.

SHM has been tapped for the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level award for its mentored-implementation model.

The award, given by the National Quality Forum and the Joint Commission marks the first time a professional society has been given the honor, according to an NQF spokeswoman.

The model links mentors with constituent hospitals to help push quality improvement models tied to transitional care, glycemic control, and VTE prevention. Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to the award announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM President Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort."

SHM has been tapped for the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level award for its mentored-implementation model.

The award, given by the National Quality Forum and the Joint Commission marks the first time a professional society has been given the honor, according to an NQF spokeswoman.

The model links mentors with constituent hospitals to help push quality improvement models tied to transitional care, glycemic control, and VTE prevention. Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to the award announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM President Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort."

SHM has been tapped for the 2011 John M. Eisenberg Innovation in Patient Safety and Quality at the National Level award for its mentored-implementation model.

The award, given by the National Quality Forum and the Joint Commission marks the first time a professional society has been given the honor, according to an NQF spokeswoman.

The model links mentors with constituent hospitals to help push quality improvement models tied to transitional care, glycemic control, and VTE prevention. Mentors have been put in place in more than 300 hospitals in the U.S. and Canada, according to the award announcement.

“There are significant congratulations [due] to the profession and all the people at the society who have done all the work on this,” says SHM President Joseph Ming-Wah Li, MD, SFHM. “Part of what we’ve been saying all along is that quality is important. In terms of teaching quality—it’s a real team effort."

Hospitalists should view a new American College of Physicians (ACP) list of three dozen commonly overused clinical tests that offer lower value as an opportunity to review their use of screening and diagnostic tools, according to one of the list's authors.

Jeff Wiese, MD, SFHM, professor of medicine and residency program director at Tulane University Health Sciences Center in New Orleans, coauthored research published in January in the Annals of Internal Medicine that he says represents clinical situations in which tests have historically been administered but, upon further review, do not reflect "high-value care."

"Nobody is trying to waste money," says Dr. Wiese, a former president of SHM who adds that physicians over time might learn that tests that once offered higher value may no longer do so. "Only by critically reviewing our habits are we able to make the necessary adjustments to ensure we are delivering high-value, cost-conscious care."

ACP convened an ad hoc workgroup of internal-medicine specialists to review lower-value tests; the list that the team came up with includes:

• Repeat screening ultrasonography for abdominal aortic aneurysm following a negative study; 
• Screening for prostate cancer in men older than 75 or with a life expectancy of less than 10 years; and
• Performing serologic testing for suspected early Lyme disease.

Dr. Wiese emphasizes that decisions regarding "cost-conscious care" must be interpreted in the context of the specific patient in front of them.

"There is no decision rule that applies to all patients," he says. "The tests addressed in the article are examples of tests that do not routinely offer high value, but this is not to say that there are not specific circumstances when they might be useful."

Hospitalists should view a new American College of Physicians (ACP) list of three dozen commonly overused clinical tests that offer lower value as an opportunity to review their use of screening and diagnostic tools, according to one of the list's authors.

Jeff Wiese, MD, SFHM, professor of medicine and residency program director at Tulane University Health Sciences Center in New Orleans, coauthored research published in January in the Annals of Internal Medicine that he says represents clinical situations in which tests have historically been administered but, upon further review, do not reflect "high-value care."

"Nobody is trying to waste money," says Dr. Wiese, a former president of SHM who adds that physicians over time might learn that tests that once offered higher value may no longer do so. "Only by critically reviewing our habits are we able to make the necessary adjustments to ensure we are delivering high-value, cost-conscious care."

ACP convened an ad hoc workgroup of internal-medicine specialists to review lower-value tests; the list that the team came up with includes:

• Repeat screening ultrasonography for abdominal aortic aneurysm following a negative study; 
• Screening for prostate cancer in men older than 75 or with a life expectancy of less than 10 years; and
• Performing serologic testing for suspected early Lyme disease.

Dr. Wiese emphasizes that decisions regarding "cost-conscious care" must be interpreted in the context of the specific patient in front of them.

"There is no decision rule that applies to all patients," he says. "The tests addressed in the article are examples of tests that do not routinely offer high value, but this is not to say that there are not specific circumstances when they might be useful."

Hospitalists should view a new American College of Physicians (ACP) list of three dozen commonly overused clinical tests that offer lower value as an opportunity to review their use of screening and diagnostic tools, according to one of the list's authors.

Jeff Wiese, MD, SFHM, professor of medicine and residency program director at Tulane University Health Sciences Center in New Orleans, coauthored research published in January in the Annals of Internal Medicine that he says represents clinical situations in which tests have historically been administered but, upon further review, do not reflect "high-value care."

"Nobody is trying to waste money," says Dr. Wiese, a former president of SHM who adds that physicians over time might learn that tests that once offered higher value may no longer do so. "Only by critically reviewing our habits are we able to make the necessary adjustments to ensure we are delivering high-value, cost-conscious care."

ACP convened an ad hoc workgroup of internal-medicine specialists to review lower-value tests; the list that the team came up with includes:

• Repeat screening ultrasonography for abdominal aortic aneurysm following a negative study; 
• Screening for prostate cancer in men older than 75 or with a life expectancy of less than 10 years; and
• Performing serologic testing for suspected early Lyme disease.

Dr. Wiese emphasizes that decisions regarding "cost-conscious care" must be interpreted in the context of the specific patient in front of them.

"There is no decision rule that applies to all patients," he says. "The tests addressed in the article are examples of tests that do not routinely offer high value, but this is not to say that there are not specific circumstances when they might be useful."

Clinical question: What is the current level of continuity of care, and what factors affect continuity of care in the hospital setting? Has this changed with increasing use of hospitalists and limits on residency duty hours?

Background: Outpatient continuity of care leads to lower costs, better quality of life, and less emergency room use. Recent changes in residency hours have increased hand-offs and decreased inpatient continuity, but to what extent is unknown.

Study design: Retrospective cohort of 5% of Medicare claims data (530,000 patients in all) from 1996 to 2006, including patients admitted for COPD, congestive heart failure, or pneumonia who were cared for by a general internist or family practitioner.

Setting: Nationwide in the U.S.

Synopsis: The authors defined patients as having a primary-care physician (PCP) if they had three billed visits with the PCP in the last year, hospitalists as those who derived at least 90% of their Medicare claims from inpatient billing, and other generalists as those who met criteria as a generalist but did not fit these categories. Inpatient continuity of care decreased to 59% of patients seeing a single physician in the hospital in 2006 from 71% in 1996, with an accompanying decrease in the length of stay of one full day. There were large variations by geographic region, population size, and hospital characteristics. Patients cared for by hospitalists had slightly better continuity of care than those cared for by nonhospitalist generalists, and those who were cared for by both hospitalists and nonhospitalist generalists had the worst continuity of care. Having a PCP was associated with increased discontinuity of care as an inpatient, perhaps because of individual members of a practice rounding on all of the practice’s inpatients.

Bottom line: Patients were 5% less likely per year between 1996 and 2006 to have a single physician be their primary caregiver in the hospital, but the rise of the hospitalist movement does not seem to be the cause.

Citation: Fletcher KE, Sharma G, Zhang D, Kuo YF, Goodwin JS. Trends in inpatient continuity of care for a cohort of Medicare patients 1996-2006. J Hosp Med. 2011;6:441-447.

For more physician reviews of HM-relevant literature, visit our website.

Clinical question: What is the current level of continuity of care, and what factors affect continuity of care in the hospital setting? Has this changed with increasing use of hospitalists and limits on residency duty hours?

Background: Outpatient continuity of care leads to lower costs, better quality of life, and less emergency room use. Recent changes in residency hours have increased hand-offs and decreased inpatient continuity, but to what extent is unknown.

Study design: Retrospective cohort of 5% of Medicare claims data (530,000 patients in all) from 1996 to 2006, including patients admitted for COPD, congestive heart failure, or pneumonia who were cared for by a general internist or family practitioner.

Setting: Nationwide in the U.S.

Synopsis: The authors defined patients as having a primary-care physician (PCP) if they had three billed visits with the PCP in the last year, hospitalists as those who derived at least 90% of their Medicare claims from inpatient billing, and other generalists as those who met criteria as a generalist but did not fit these categories. Inpatient continuity of care decreased to 59% of patients seeing a single physician in the hospital in 2006 from 71% in 1996, with an accompanying decrease in the length of stay of one full day. There were large variations by geographic region, population size, and hospital characteristics. Patients cared for by hospitalists had slightly better continuity of care than those cared for by nonhospitalist generalists, and those who were cared for by both hospitalists and nonhospitalist generalists had the worst continuity of care. Having a PCP was associated with increased discontinuity of care as an inpatient, perhaps because of individual members of a practice rounding on all of the practice’s inpatients.

Bottom line: Patients were 5% less likely per year between 1996 and 2006 to have a single physician be their primary caregiver in the hospital, but the rise of the hospitalist movement does not seem to be the cause.

Citation: Fletcher KE, Sharma G, Zhang D, Kuo YF, Goodwin JS. Trends in inpatient continuity of care for a cohort of Medicare patients 1996-2006. J Hosp Med. 2011;6:441-447.

For more physician reviews of HM-relevant literature, visit our website.

Clinical question: What is the current level of continuity of care, and what factors affect continuity of care in the hospital setting? Has this changed with increasing use of hospitalists and limits on residency duty hours?

Background: Outpatient continuity of care leads to lower costs, better quality of life, and less emergency room use. Recent changes in residency hours have increased hand-offs and decreased inpatient continuity, but to what extent is unknown.

Study design: Retrospective cohort of 5% of Medicare claims data (530,000 patients in all) from 1996 to 2006, including patients admitted for COPD, congestive heart failure, or pneumonia who were cared for by a general internist or family practitioner.

Setting: Nationwide in the U.S.

Synopsis: The authors defined patients as having a primary-care physician (PCP) if they had three billed visits with the PCP in the last year, hospitalists as those who derived at least 90% of their Medicare claims from inpatient billing, and other generalists as those who met criteria as a generalist but did not fit these categories. Inpatient continuity of care decreased to 59% of patients seeing a single physician in the hospital in 2006 from 71% in 1996, with an accompanying decrease in the length of stay of one full day. There were large variations by geographic region, population size, and hospital characteristics. Patients cared for by hospitalists had slightly better continuity of care than those cared for by nonhospitalist generalists, and those who were cared for by both hospitalists and nonhospitalist generalists had the worst continuity of care. Having a PCP was associated with increased discontinuity of care as an inpatient, perhaps because of individual members of a practice rounding on all of the practice’s inpatients.

Bottom line: Patients were 5% less likely per year between 1996 and 2006 to have a single physician be their primary caregiver in the hospital, but the rise of the hospitalist movement does not seem to be the cause.

Citation: Fletcher KE, Sharma G, Zhang D, Kuo YF, Goodwin JS. Trends in inpatient continuity of care for a cohort of Medicare patients 1996-2006. J Hosp Med. 2011;6:441-447.

For more physician reviews of HM-relevant literature, visit our website.

The annual meetings of the American College of Cardiology and the American Heart Association have been the centerpiece for the international exchange of ideas in clinical and basic cardiology for the last half century. They have attracted research scientists from around the world as a result of their preeminence as a platform for the presentation of new concepts.

They provided the setting for Mason Sones to show the first direct angiographic imaging of the coronary artery, for Andreis Grunzig to demonstrate the first percutaneous dilatation of the coronary artery, and for Michel Mirowski to present the first demonstration of the automatic implanted defibrillator. Those events caused gasps in the audience as we all saw, for the first time, a major breakthrough in cardiovascular medicine.

The scramble to get onto that platform or to be in that audience when the newest discovery was presented drew large audiences. The decrease in attendance in the past few years can be viewed as an index of the decrease in the importance of that platform.

The decreased attendance in the AHA and ACC annual scientific sessions provides ample evidence of the reduced role of American leadership and the ascendancy of European leadership in the world of cardiology. As the attendance at American meetings has ebbed, the European Society of Cardiology has seen a progressive increase in attendance of its annual meeting.

The AHA reached its highest attendance in the later part of the last century when its professional attendance in 1999 topped just over 20,000. It gradually slipped to 19,169 in 2010, and was 15,553 in Orlando in 2011. The ACC professional attendance has also fallen, from 18,542 in 2008 to 12,980 in 2011. At the same time, the attendance at the European Society of Cardiology has increased from 18,413 in 2002 in Berlin to almost 27,080 professional attendees in 2011 in Paris.

This decrease has not been observed in all American medical specialties. The Radiological Society of North America has had approximately 27,000 professional attendees for the last 5 years, and it advertises nearly eight football fields of exhibits.

One factor limiting attendance at some meetings is the expense, including the increase in admission fees, which now have gotten well into the four-figure level even if you are a member.

One of the most striking changes at the recent AHA and ACC meetings was the stark decrease in exhibitors. Exhibits that seemed to go on for miles in previous years, requiring rest stops at coffee stands along the way, have now became accessible with a casual walk. Many of the high-tech exhibitors either shrank their exhibit space or were entirely absent. Attendance and the number of exhibitors at the recent AHA meeting were impacted by the annual meeting of Transcatheter Cardiovascular Therapeutics, which had more than 12,000 attendees and was being held almost simultaneously a continent away. In order to fill the exhibition space at the recent AHA meeting, booth space was given over to displays of costume jewelry and pashmina scarves.

It is estimated by representatives of the ACC that international attendance at American meetings has decreased by at least one-third. This decrease is open to different interpretations. It has become increasingly difficult, for example, for many Asian and Eastern European cardiologists to obtain U.S. visas. But the fact that the Europeans do have an excellent meeting on their own soil has made that meeting more accessible to them. It is also clear that more Asian and American cardiologists are attending the European meeting. Part of this attraction has been related to a friendlier environment for the performance and consequent presentation of clinical trials in Europe.

The decrease in attendance at the American meetings is, in large part, a result of the balkanization of the "big tent" of cardiology. The creation of specialty associations by electrophysiologists, interventionalists, and heart failure specialists, to name but a few, has impacted on the appeal of – and need to engage in – the large annual meeting in order to satisfy professional requirements. Specialty cardiologists now have not only their own meeting platforms, but also their own specialty journals, which are in direct competition with JACC and Circulation.

What is lost, however, is the integrated educational experience that the practicing cardiologist needs in order to bring the entirety of cardiovascular science to the individual patient. When the field of cardiology was smaller and its scientific and clinical horizons were nearer at hand, this could be accomplished at one meeting.

We have, unfortunately, outgrown our "tent," but the Internet is now there to help us. Access to the meeting’s scientific presentations is now readily available through a variety of electronic media sites, including Cardiology News.

The annual meetings of the American College of Cardiology and the American Heart Association have been the centerpiece for the international exchange of ideas in clinical and basic cardiology for the last half century. They have attracted research scientists from around the world as a result of their preeminence as a platform for the presentation of new concepts.

They provided the setting for Mason Sones to show the first direct angiographic imaging of the coronary artery, for Andreis Grunzig to demonstrate the first percutaneous dilatation of the coronary artery, and for Michel Mirowski to present the first demonstration of the automatic implanted defibrillator. Those events caused gasps in the audience as we all saw, for the first time, a major breakthrough in cardiovascular medicine.

The scramble to get onto that platform or to be in that audience when the newest discovery was presented drew large audiences. The decrease in attendance in the past few years can be viewed as an index of the decrease in the importance of that platform.

The decreased attendance in the AHA and ACC annual scientific sessions provides ample evidence of the reduced role of American leadership and the ascendancy of European leadership in the world of cardiology. As the attendance at American meetings has ebbed, the European Society of Cardiology has seen a progressive increase in attendance of its annual meeting.

The AHA reached its highest attendance in the later part of the last century when its professional attendance in 1999 topped just over 20,000. It gradually slipped to 19,169 in 2010, and was 15,553 in Orlando in 2011. The ACC professional attendance has also fallen, from 18,542 in 2008 to 12,980 in 2011. At the same time, the attendance at the European Society of Cardiology has increased from 18,413 in 2002 in Berlin to almost 27,080 professional attendees in 2011 in Paris.

This decrease has not been observed in all American medical specialties. The Radiological Society of North America has had approximately 27,000 professional attendees for the last 5 years, and it advertises nearly eight football fields of exhibits.

One factor limiting attendance at some meetings is the expense, including the increase in admission fees, which now have gotten well into the four-figure level even if you are a member.

One of the most striking changes at the recent AHA and ACC meetings was the stark decrease in exhibitors. Exhibits that seemed to go on for miles in previous years, requiring rest stops at coffee stands along the way, have now became accessible with a casual walk. Many of the high-tech exhibitors either shrank their exhibit space or were entirely absent. Attendance and the number of exhibitors at the recent AHA meeting were impacted by the annual meeting of Transcatheter Cardiovascular Therapeutics, which had more than 12,000 attendees and was being held almost simultaneously a continent away. In order to fill the exhibition space at the recent AHA meeting, booth space was given over to displays of costume jewelry and pashmina scarves.

It is estimated by representatives of the ACC that international attendance at American meetings has decreased by at least one-third. This decrease is open to different interpretations. It has become increasingly difficult, for example, for many Asian and Eastern European cardiologists to obtain U.S. visas. But the fact that the Europeans do have an excellent meeting on their own soil has made that meeting more accessible to them. It is also clear that more Asian and American cardiologists are attending the European meeting. Part of this attraction has been related to a friendlier environment for the performance and consequent presentation of clinical trials in Europe.

The decrease in attendance at the American meetings is, in large part, a result of the balkanization of the "big tent" of cardiology. The creation of specialty associations by electrophysiologists, interventionalists, and heart failure specialists, to name but a few, has impacted on the appeal of – and need to engage in – the large annual meeting in order to satisfy professional requirements. Specialty cardiologists now have not only their own meeting platforms, but also their own specialty journals, which are in direct competition with JACC and Circulation.

What is lost, however, is the integrated educational experience that the practicing cardiologist needs in order to bring the entirety of cardiovascular science to the individual patient. When the field of cardiology was smaller and its scientific and clinical horizons were nearer at hand, this could be accomplished at one meeting.

We have, unfortunately, outgrown our "tent," but the Internet is now there to help us. Access to the meeting’s scientific presentations is now readily available through a variety of electronic media sites, including Cardiology News.

The annual meetings of the American College of Cardiology and the American Heart Association have been the centerpiece for the international exchange of ideas in clinical and basic cardiology for the last half century. They have attracted research scientists from around the world as a result of their preeminence as a platform for the presentation of new concepts.

They provided the setting for Mason Sones to show the first direct angiographic imaging of the coronary artery, for Andreis Grunzig to demonstrate the first percutaneous dilatation of the coronary artery, and for Michel Mirowski to present the first demonstration of the automatic implanted defibrillator. Those events caused gasps in the audience as we all saw, for the first time, a major breakthrough in cardiovascular medicine.

The scramble to get onto that platform or to be in that audience when the newest discovery was presented drew large audiences. The decrease in attendance in the past few years can be viewed as an index of the decrease in the importance of that platform.

The decreased attendance in the AHA and ACC annual scientific sessions provides ample evidence of the reduced role of American leadership and the ascendancy of European leadership in the world of cardiology. As the attendance at American meetings has ebbed, the European Society of Cardiology has seen a progressive increase in attendance of its annual meeting.

The AHA reached its highest attendance in the later part of the last century when its professional attendance in 1999 topped just over 20,000. It gradually slipped to 19,169 in 2010, and was 15,553 in Orlando in 2011. The ACC professional attendance has also fallen, from 18,542 in 2008 to 12,980 in 2011. At the same time, the attendance at the European Society of Cardiology has increased from 18,413 in 2002 in Berlin to almost 27,080 professional attendees in 2011 in Paris.

This decrease has not been observed in all American medical specialties. The Radiological Society of North America has had approximately 27,000 professional attendees for the last 5 years, and it advertises nearly eight football fields of exhibits.

One factor limiting attendance at some meetings is the expense, including the increase in admission fees, which now have gotten well into the four-figure level even if you are a member.

One of the most striking changes at the recent AHA and ACC meetings was the stark decrease in exhibitors. Exhibits that seemed to go on for miles in previous years, requiring rest stops at coffee stands along the way, have now became accessible with a casual walk. Many of the high-tech exhibitors either shrank their exhibit space or were entirely absent. Attendance and the number of exhibitors at the recent AHA meeting were impacted by the annual meeting of Transcatheter Cardiovascular Therapeutics, which had more than 12,000 attendees and was being held almost simultaneously a continent away. In order to fill the exhibition space at the recent AHA meeting, booth space was given over to displays of costume jewelry and pashmina scarves.

It is estimated by representatives of the ACC that international attendance at American meetings has decreased by at least one-third. This decrease is open to different interpretations. It has become increasingly difficult, for example, for many Asian and Eastern European cardiologists to obtain U.S. visas. But the fact that the Europeans do have an excellent meeting on their own soil has made that meeting more accessible to them. It is also clear that more Asian and American cardiologists are attending the European meeting. Part of this attraction has been related to a friendlier environment for the performance and consequent presentation of clinical trials in Europe.

The decrease in attendance at the American meetings is, in large part, a result of the balkanization of the "big tent" of cardiology. The creation of specialty associations by electrophysiologists, interventionalists, and heart failure specialists, to name but a few, has impacted on the appeal of – and need to engage in – the large annual meeting in order to satisfy professional requirements. Specialty cardiologists now have not only their own meeting platforms, but also their own specialty journals, which are in direct competition with JACC and Circulation.

What is lost, however, is the integrated educational experience that the practicing cardiologist needs in order to bring the entirety of cardiovascular science to the individual patient. When the field of cardiology was smaller and its scientific and clinical horizons were nearer at hand, this could be accomplished at one meeting.

We have, unfortunately, outgrown our "tent," but the Internet is now there to help us. Access to the meeting’s scientific presentations is now readily available through a variety of electronic media sites, including Cardiology News.

Overall 5-year survival in children with acute lymphoblastic leukemia improved from 83.7% to 90.4% between the early 1990s and the early 2000s, according to a report published online March 12 in the Journal of Clinical Oncology.

Five-year survival improved by 30%-50% across all subgroups of patients during this interval, with one discouraging exception: It remained steady and much lower in infants aged less than 1 year, said Dr. Stephen P. Hunger of the University of Colorado Cancer Center and his associates in the Children’s Oncology Group (COG).

The investigators assessed outcomes in 21,626 children and adolescents participating in 36 ALL clinical trials in 1990-2005, which they described as "the largest childhood ALL cohort ever reported." The COG includes more than 200 member institutions in the United States, Canada, and other countries, which together have enrolled 56% of all cases of pediatric ALL that occurred in the United States between 1990 and 2005 in clinical trials.

"Thus, our results are representative of survival following contemporary therapy in the U.S." and differ somewhat from those of other large groups such as the National Cancer Institute’s SEER program, they said.

Dr. Hunger and his colleagues divided this cohort into three similar-sized groups in three eras: 7,304 patients treated in 1990-1994; 7,169 treated in 1995-1999; and 7,153 treated in 2000-2005. The median follow-up was 9.13 years, 8.02 years, and 5.35 years, respectively.

Most (92%) of these study subjects were treated in the United States, with 6% treated in Canada and 2% treated elsewhere.

Overall 5-year survival increased from 83.7% in the first era to 87.7% in the second and to 90.4% in the third. "We believe that the major reason for improved survival was decreased risk of relapse," they said (J. Clin. Oncol. 2012 March 12 [doi:10.1200/JCO.20911.37.8018]).

This is because the rate of deaths from relapse decreased markedly during this interval, from 43% in 1990-1994 to 27% in 2000-2005.

Among infants, the 5-year risk of death changed little, at 52.1% in 1990-1994 and 50.3% in 2000-2005. During the study period, "the COG pursued several strategies to attempt to increase survival for infants with ALL. Chemotherapy treatment was intensified significantly" in two clinical trials, while stem-cell transplantation was explored in others.

Stem-cell therapy was not found to be beneficial in infants in these studies, and chemotherapy intensification raised the rate of treatment-related death to the same degree that it lowered the rate of death from disease progression, with no net improvement in survival.

"Infant ALL is a unique high-risk subset that requires new therapeutic strategies," the researchers said.

Five-year survival improved 30%-50% across all other subgroups of patients: in all age groups (except infants), in both sexes, in all races and ethnicities, in patients with B-cell or T-cell disease, in patients with average-risk or high-risk profiles, and across all features of ALL according to NCI criteria.

However, the risk of death still remained higher in patients aged 10 or older, compared with those aged 1-10, higher in boys than in girls, higher in blacks and Hispanics than in whites, and higher in T-cell than in B-cell disease. Risk of death was two- to fourfold higher in patients high-risk than in average-risk patients.

It was encouraging that the "racial gap" in outcomes between whites and nonwhites narrowed during the study period. For example, the absolute difference in 5-year survival between whites and blacks declined from 11.0% in 1990-1994 to only 3.3% in 2000-2005. Racial differences between whites and nonwhites in ALL biology are still evident, with black and Hispanic patients being more likely than whites to carry higher-risk forms of the disease or higher-risk genetic profiles, the investigators noted.

A total of 36% of the ALL deaths in these study subjects occurred in patients who were at average risk. "Thus, efforts to decrease ALL deaths must focus both on high-risk patient subsets and on the large subset of patients with favorable clinical characteristics," Dr. Hunger and his associates said.

Based on their data, the researchers also "anticipate significant improvements in 10-year survival."

Children’s Oncology Group studies are supported by the National Cancer Institute. Dr. Hunger reported no financial conflicts of interest. One associate reported ties to EUSA Pharma, Sanofi-Aventis, Teva Pharmaceutical Industries, Bristol-Myers Squibb, Enzon Pharmaceuticals, Sigma Tau Pharmaceuticals, and Genzyme.

Overall 5-year survival in children with acute lymphoblastic leukemia improved from 83.7% to 90.4% between the early 1990s and the early 2000s, according to a report published online March 12 in the Journal of Clinical Oncology.

Five-year survival improved by 30%-50% across all subgroups of patients during this interval, with one discouraging exception: It remained steady and much lower in infants aged less than 1 year, said Dr. Stephen P. Hunger of the University of Colorado Cancer Center and his associates in the Children’s Oncology Group (COG).

The investigators assessed outcomes in 21,626 children and adolescents participating in 36 ALL clinical trials in 1990-2005, which they described as "the largest childhood ALL cohort ever reported." The COG includes more than 200 member institutions in the United States, Canada, and other countries, which together have enrolled 56% of all cases of pediatric ALL that occurred in the United States between 1990 and 2005 in clinical trials.

"Thus, our results are representative of survival following contemporary therapy in the U.S." and differ somewhat from those of other large groups such as the National Cancer Institute’s SEER program, they said.

Dr. Hunger and his colleagues divided this cohort into three similar-sized groups in three eras: 7,304 patients treated in 1990-1994; 7,169 treated in 1995-1999; and 7,153 treated in 2000-2005. The median follow-up was 9.13 years, 8.02 years, and 5.35 years, respectively.

Most (92%) of these study subjects were treated in the United States, with 6% treated in Canada and 2% treated elsewhere.

Overall 5-year survival increased from 83.7% in the first era to 87.7% in the second and to 90.4% in the third. "We believe that the major reason for improved survival was decreased risk of relapse," they said (J. Clin. Oncol. 2012 March 12 [doi:10.1200/JCO.20911.37.8018]).

This is because the rate of deaths from relapse decreased markedly during this interval, from 43% in 1990-1994 to 27% in 2000-2005.

Among infants, the 5-year risk of death changed little, at 52.1% in 1990-1994 and 50.3% in 2000-2005. During the study period, "the COG pursued several strategies to attempt to increase survival for infants with ALL. Chemotherapy treatment was intensified significantly" in two clinical trials, while stem-cell transplantation was explored in others.

Stem-cell therapy was not found to be beneficial in infants in these studies, and chemotherapy intensification raised the rate of treatment-related death to the same degree that it lowered the rate of death from disease progression, with no net improvement in survival.

"Infant ALL is a unique high-risk subset that requires new therapeutic strategies," the researchers said.

Five-year survival improved 30%-50% across all other subgroups of patients: in all age groups (except infants), in both sexes, in all races and ethnicities, in patients with B-cell or T-cell disease, in patients with average-risk or high-risk profiles, and across all features of ALL according to NCI criteria.

However, the risk of death still remained higher in patients aged 10 or older, compared with those aged 1-10, higher in boys than in girls, higher in blacks and Hispanics than in whites, and higher in T-cell than in B-cell disease. Risk of death was two- to fourfold higher in patients high-risk than in average-risk patients.

It was encouraging that the "racial gap" in outcomes between whites and nonwhites narrowed during the study period. For example, the absolute difference in 5-year survival between whites and blacks declined from 11.0% in 1990-1994 to only 3.3% in 2000-2005. Racial differences between whites and nonwhites in ALL biology are still evident, with black and Hispanic patients being more likely than whites to carry higher-risk forms of the disease or higher-risk genetic profiles, the investigators noted.

A total of 36% of the ALL deaths in these study subjects occurred in patients who were at average risk. "Thus, efforts to decrease ALL deaths must focus both on high-risk patient subsets and on the large subset of patients with favorable clinical characteristics," Dr. Hunger and his associates said.

Based on their data, the researchers also "anticipate significant improvements in 10-year survival."

Children’s Oncology Group studies are supported by the National Cancer Institute. Dr. Hunger reported no financial conflicts of interest. One associate reported ties to EUSA Pharma, Sanofi-Aventis, Teva Pharmaceutical Industries, Bristol-Myers Squibb, Enzon Pharmaceuticals, Sigma Tau Pharmaceuticals, and Genzyme.

Overall 5-year survival in children with acute lymphoblastic leukemia improved from 83.7% to 90.4% between the early 1990s and the early 2000s, according to a report published online March 12 in the Journal of Clinical Oncology.

Five-year survival improved by 30%-50% across all subgroups of patients during this interval, with one discouraging exception: It remained steady and much lower in infants aged less than 1 year, said Dr. Stephen P. Hunger of the University of Colorado Cancer Center and his associates in the Children’s Oncology Group (COG).

The investigators assessed outcomes in 21,626 children and adolescents participating in 36 ALL clinical trials in 1990-2005, which they described as "the largest childhood ALL cohort ever reported." The COG includes more than 200 member institutions in the United States, Canada, and other countries, which together have enrolled 56% of all cases of pediatric ALL that occurred in the United States between 1990 and 2005 in clinical trials.

"Thus, our results are representative of survival following contemporary therapy in the U.S." and differ somewhat from those of other large groups such as the National Cancer Institute’s SEER program, they said.

Dr. Hunger and his colleagues divided this cohort into three similar-sized groups in three eras: 7,304 patients treated in 1990-1994; 7,169 treated in 1995-1999; and 7,153 treated in 2000-2005. The median follow-up was 9.13 years, 8.02 years, and 5.35 years, respectively.

Most (92%) of these study subjects were treated in the United States, with 6% treated in Canada and 2% treated elsewhere.

Overall 5-year survival increased from 83.7% in the first era to 87.7% in the second and to 90.4% in the third. "We believe that the major reason for improved survival was decreased risk of relapse," they said (J. Clin. Oncol. 2012 March 12 [doi:10.1200/JCO.20911.37.8018]).

This is because the rate of deaths from relapse decreased markedly during this interval, from 43% in 1990-1994 to 27% in 2000-2005.

Among infants, the 5-year risk of death changed little, at 52.1% in 1990-1994 and 50.3% in 2000-2005. During the study period, "the COG pursued several strategies to attempt to increase survival for infants with ALL. Chemotherapy treatment was intensified significantly" in two clinical trials, while stem-cell transplantation was explored in others.

Stem-cell therapy was not found to be beneficial in infants in these studies, and chemotherapy intensification raised the rate of treatment-related death to the same degree that it lowered the rate of death from disease progression, with no net improvement in survival.

"Infant ALL is a unique high-risk subset that requires new therapeutic strategies," the researchers said.

Five-year survival improved 30%-50% across all other subgroups of patients: in all age groups (except infants), in both sexes, in all races and ethnicities, in patients with B-cell or T-cell disease, in patients with average-risk or high-risk profiles, and across all features of ALL according to NCI criteria.

However, the risk of death still remained higher in patients aged 10 or older, compared with those aged 1-10, higher in boys than in girls, higher in blacks and Hispanics than in whites, and higher in T-cell than in B-cell disease. Risk of death was two- to fourfold higher in patients high-risk than in average-risk patients.

It was encouraging that the "racial gap" in outcomes between whites and nonwhites narrowed during the study period. For example, the absolute difference in 5-year survival between whites and blacks declined from 11.0% in 1990-1994 to only 3.3% in 2000-2005. Racial differences between whites and nonwhites in ALL biology are still evident, with black and Hispanic patients being more likely than whites to carry higher-risk forms of the disease or higher-risk genetic profiles, the investigators noted.

A total of 36% of the ALL deaths in these study subjects occurred in patients who were at average risk. "Thus, efforts to decrease ALL deaths must focus both on high-risk patient subsets and on the large subset of patients with favorable clinical characteristics," Dr. Hunger and his associates said.

Based on their data, the researchers also "anticipate significant improvements in 10-year survival."

Children’s Oncology Group studies are supported by the National Cancer Institute. Dr. Hunger reported no financial conflicts of interest. One associate reported ties to EUSA Pharma, Sanofi-Aventis, Teva Pharmaceutical Industries, Bristol-Myers Squibb, Enzon Pharmaceuticals, Sigma Tau Pharmaceuticals, and Genzyme.

The Food and Drug Administration's announcement that the labeling of statins will now note their potential for raising a patient’s blood sugar and glycosylated hemoglobin levels is a reminder that, despite their relative safety, statin treatment poses some level of risk and hence should not be prescribed indiscriminately, experts said.

On the other hand, the risk for blood sugar elevation is modest enough that for the vast majority of patients who have significant cardiovascular disease (CVD) risk, the potential benefit from statin treatment continues to far outweigh the risk patients might face from statin-induced hyperglycemia, according to several experts interviewed for this article. Patients with cardiovascular disease risk who could remain on statins include those who have already had a cardiovascular event, the secondary prevention population, and patients who already have diabetes, considered a coronary risk equivalent because of the sizeable risk that diabetes confers for a future cardiovascular event.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease."

Boosted hyperglycemia that pushes a person’s fasting plasma glucose level to 126 mg/dL or above, the range diagnosed as type 2 diabetes, "is probably the most frequent quantifiable harm from statins" but is still uncommon, noted Dr. Jennifer G. Robinson, professor of medicine and epidemiology at the University of Iowa in Iowa City. She estimated that of the 10%-15% of patients who will develop type 2 diabetes over a period of several years on statin treatment, roughly 1 new case of diabetes out of every 500 incident cases will be attributable to statin treatment, based on the risk information available today.

"It's not very much. It should not change any clinician’s day to day practice in any way," said Dr. Robinson, who is also a vice-chair of the Adult Treatment Panel IV, the group assembled by the National Heart, Lung, and Blood Institute to issue new U.S. cholesterol management guidelines, expected later this year. "It just means that you don’t give a statin to everyone, not someone with a 1% risk for a cardiovascular event over the next 10 years," she said.

Primary prevention poses the most complicated issues, when physicians prescribe statins to people who have not yet had any cardiovascular event. Prescribers face the difficult question of when the risk for incident hyperglycemia triggered by a statin starts to outweigh the benefit from cardiovascular risk reduction. Further muddying the question of whom to exclude from primary prevention with statin treatment are the unknowns that shroud the effect: How do statins cause this? Which patients are most susceptible? Do different statins pose varying levels of hyperglycemia risk?

"As increasingly large populations become candidates for statin treatment, with new guidelines and new methods for CVD risk-prediction modeling, it will be very important to look at the benefit to risk ratio of treatment, including the risk for developing diabetes," said Dr. JoAnn E. Manson, professor of medicine at Harvard Medical School and chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Relatively low-risk groups of patients who are increasingly prescribed statins include adolescents, young adults, and middle-aged women, she noted. "The key is the absolute risk of CVD in these groups, more than their relative risk. In a population with a low absolute risk of CVD events, we need to look very carefully to see where the crossover occurs from net benefit to net risk of treatment."

A problem for the time being is that no good way exists for identifying what factors, beyond borderline high blood glucose at baseline, help identify patients at increased risk for developing diabetes while on statin treatment. Additional research and guidance about what level of fasting plasma glucose at baseline, before a statin regimen starts, should trigger concern, and how often plasma glucose should be monitored once a patient is on a statin, will be helpful, Dr. Manson said.

"Professional societies and expert groups should make clear recommendations about the need for routine vs. targeted glucose testing, as well as the frequency. Consensus guidelines don’t yet exist. The new statin label eliminates testing liver function. Will this be replaced by excessive testing of blood glucose, a practice that could be burdensome to patients and clinicians and drive up health care costs?" she said in an interview.

The dilemma physicians also face when deciding whether to prescribe a statin to patients toward the low end of the cardiovascular risk spectrum is that the same risk factors that might flag patients with a high risk for insulin resistance, hyperglycemia, and the development of type 2 diabetes – factors such as obesity, inadequate physical activity, elements of metabolic syndrome, and a "prediabetic" fasting plasma glucose level of 110-125 mg/dL – also function as cardiovascular disease risk factors.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease," Dr. Manson said. She recommended that patients on statin treatment at least be told to be on the alert for developing new symptoms of diabetes: frequent thirst, frequent urination, and blurred vision. "And lifestyle modifications should be intensified to reduce both diabetes and CVD risk."

"The excess risk for diabetes is concentrated in the people with fasting blood sugars in the 115- to 125-mg/dL range" said Dr. Roger S. Blumenthal, professor of medicine and director of preventive medicine at Johns Hopkins Medical Institutions in Baltimore. "A lot of those people are clearly insulin resistant. We almost always have a fasting plasma glucose [when patients are about to start on a statin] as part of a basic lipid profile. With physicians aware of the association, I think this will focus more attention on vulnerable patients in the 115- to 125-mg/dL range, who are headed for diabetes if they don’t make significant improvements in their diet and exercise habits. It’s reasonable to look at glucose and tell patients that a statin might potentially raise their blood sugar by 5-7 mg/dL, but exercising and dropping some excess weight will significantly improve their blood sugar."

Targeted use of plasma glucose testing in statin recipients who seem to have the greatest risk for developing diabetes also received endorsement from Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, in Fresno. He suggested possibly doing annual testing of patients with metabolic syndrome, those who are obese, those with a family history of diabetes, and patients who have previously shown impaired glucose tolerance on a tolerance test.

If a patient’s fasting plasma glucose began to creep up on a statin regimen, "I’d look for other reasons, such as did they gain weight?" he said. Seeing a possible hyperglycemic effect should also prompt a reassessment of whether the patient benefited from the statin, and whether they have made necessary lifestyle changes like improved diet and increased exercise. Rising blood sugar could be used to help motivate a patient to do better on lifestyle measures, and trigger a reevaluation of whether the patient is, on balance, benefiting from the statin, he said. Changing the statin used or the dosage is tricky, because no evidence exists now to support such steps.

But because the biggest signal for the prodiabetic effect of statins came in results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) (N. Engl. J. Med. 2008;359:2195-207), the current perception among at least some physicians is that rosuvastatin (Crestor) poses the biggest hyperglycemic risk. "Some physicians might consider changing [the prescribed statin] from rosuvastatin to simvastatin or atorvastatin," Dr. Blumenthal said.

The FDA took the right step in adding the hyperglycemia information to statin labeling, said Dr. Deedwania. "They give the data, and leave it up to physicians to make their own conclusions."

As a consequence of the FDA’s actions "a lot more physicians will pay attention to glucose as they put patients on statins. The evidence is consistent, and most now agree that it’s real," said Dr. Stephen J. Nicholls, a cardiologist at the Cleveland Clinic. "But these are not completely healthy people with low glucose levels who suddenly, on a statin, become diabetic. What this reinforces is that while there will continue to be a lot of people who require statin treatment, the cornerstone of treatment is lifestyle change: diet, exercise, and weight loss. There is a continuum of risk: Patients at higher risk will benefit from a statin; for patients at very low risk use lifestyle. And if you put a patient on a statin, you need to keep an eye on them."

Dr. Robinson, Dr. Manson, and Dr. Blumenthal said that they had no relevant financial disclosures. Dr. Deedwania said that he has been a consultant to Pfizer, Amarin, and Amgen. Dr. Nicholls said he has received research support from AstraZeneca and has been a consultant to AstraZeneca, Merck, and Pfizer.

The Food and Drug Administration's announcement that the labeling of statins will now note their potential for raising a patient’s blood sugar and glycosylated hemoglobin levels is a reminder that, despite their relative safety, statin treatment poses some level of risk and hence should not be prescribed indiscriminately, experts said.

On the other hand, the risk for blood sugar elevation is modest enough that for the vast majority of patients who have significant cardiovascular disease (CVD) risk, the potential benefit from statin treatment continues to far outweigh the risk patients might face from statin-induced hyperglycemia, according to several experts interviewed for this article. Patients with cardiovascular disease risk who could remain on statins include those who have already had a cardiovascular event, the secondary prevention population, and patients who already have diabetes, considered a coronary risk equivalent because of the sizeable risk that diabetes confers for a future cardiovascular event.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease."

Boosted hyperglycemia that pushes a person’s fasting plasma glucose level to 126 mg/dL or above, the range diagnosed as type 2 diabetes, "is probably the most frequent quantifiable harm from statins" but is still uncommon, noted Dr. Jennifer G. Robinson, professor of medicine and epidemiology at the University of Iowa in Iowa City. She estimated that of the 10%-15% of patients who will develop type 2 diabetes over a period of several years on statin treatment, roughly 1 new case of diabetes out of every 500 incident cases will be attributable to statin treatment, based on the risk information available today.

"It's not very much. It should not change any clinician’s day to day practice in any way," said Dr. Robinson, who is also a vice-chair of the Adult Treatment Panel IV, the group assembled by the National Heart, Lung, and Blood Institute to issue new U.S. cholesterol management guidelines, expected later this year. "It just means that you don’t give a statin to everyone, not someone with a 1% risk for a cardiovascular event over the next 10 years," she said.

Primary prevention poses the most complicated issues, when physicians prescribe statins to people who have not yet had any cardiovascular event. Prescribers face the difficult question of when the risk for incident hyperglycemia triggered by a statin starts to outweigh the benefit from cardiovascular risk reduction. Further muddying the question of whom to exclude from primary prevention with statin treatment are the unknowns that shroud the effect: How do statins cause this? Which patients are most susceptible? Do different statins pose varying levels of hyperglycemia risk?

"As increasingly large populations become candidates for statin treatment, with new guidelines and new methods for CVD risk-prediction modeling, it will be very important to look at the benefit to risk ratio of treatment, including the risk for developing diabetes," said Dr. JoAnn E. Manson, professor of medicine at Harvard Medical School and chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Relatively low-risk groups of patients who are increasingly prescribed statins include adolescents, young adults, and middle-aged women, she noted. "The key is the absolute risk of CVD in these groups, more than their relative risk. In a population with a low absolute risk of CVD events, we need to look very carefully to see where the crossover occurs from net benefit to net risk of treatment."

A problem for the time being is that no good way exists for identifying what factors, beyond borderline high blood glucose at baseline, help identify patients at increased risk for developing diabetes while on statin treatment. Additional research and guidance about what level of fasting plasma glucose at baseline, before a statin regimen starts, should trigger concern, and how often plasma glucose should be monitored once a patient is on a statin, will be helpful, Dr. Manson said.

"Professional societies and expert groups should make clear recommendations about the need for routine vs. targeted glucose testing, as well as the frequency. Consensus guidelines don’t yet exist. The new statin label eliminates testing liver function. Will this be replaced by excessive testing of blood glucose, a practice that could be burdensome to patients and clinicians and drive up health care costs?" she said in an interview.

The dilemma physicians also face when deciding whether to prescribe a statin to patients toward the low end of the cardiovascular risk spectrum is that the same risk factors that might flag patients with a high risk for insulin resistance, hyperglycemia, and the development of type 2 diabetes – factors such as obesity, inadequate physical activity, elements of metabolic syndrome, and a "prediabetic" fasting plasma glucose level of 110-125 mg/dL – also function as cardiovascular disease risk factors.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease," Dr. Manson said. She recommended that patients on statin treatment at least be told to be on the alert for developing new symptoms of diabetes: frequent thirst, frequent urination, and blurred vision. "And lifestyle modifications should be intensified to reduce both diabetes and CVD risk."

"The excess risk for diabetes is concentrated in the people with fasting blood sugars in the 115- to 125-mg/dL range" said Dr. Roger S. Blumenthal, professor of medicine and director of preventive medicine at Johns Hopkins Medical Institutions in Baltimore. "A lot of those people are clearly insulin resistant. We almost always have a fasting plasma glucose [when patients are about to start on a statin] as part of a basic lipid profile. With physicians aware of the association, I think this will focus more attention on vulnerable patients in the 115- to 125-mg/dL range, who are headed for diabetes if they don’t make significant improvements in their diet and exercise habits. It’s reasonable to look at glucose and tell patients that a statin might potentially raise their blood sugar by 5-7 mg/dL, but exercising and dropping some excess weight will significantly improve their blood sugar."

Targeted use of plasma glucose testing in statin recipients who seem to have the greatest risk for developing diabetes also received endorsement from Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, in Fresno. He suggested possibly doing annual testing of patients with metabolic syndrome, those who are obese, those with a family history of diabetes, and patients who have previously shown impaired glucose tolerance on a tolerance test.

If a patient’s fasting plasma glucose began to creep up on a statin regimen, "I’d look for other reasons, such as did they gain weight?" he said. Seeing a possible hyperglycemic effect should also prompt a reassessment of whether the patient benefited from the statin, and whether they have made necessary lifestyle changes like improved diet and increased exercise. Rising blood sugar could be used to help motivate a patient to do better on lifestyle measures, and trigger a reevaluation of whether the patient is, on balance, benefiting from the statin, he said. Changing the statin used or the dosage is tricky, because no evidence exists now to support such steps.

But because the biggest signal for the prodiabetic effect of statins came in results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) (N. Engl. J. Med. 2008;359:2195-207), the current perception among at least some physicians is that rosuvastatin (Crestor) poses the biggest hyperglycemic risk. "Some physicians might consider changing [the prescribed statin] from rosuvastatin to simvastatin or atorvastatin," Dr. Blumenthal said.

The FDA took the right step in adding the hyperglycemia information to statin labeling, said Dr. Deedwania. "They give the data, and leave it up to physicians to make their own conclusions."

As a consequence of the FDA’s actions "a lot more physicians will pay attention to glucose as they put patients on statins. The evidence is consistent, and most now agree that it’s real," said Dr. Stephen J. Nicholls, a cardiologist at the Cleveland Clinic. "But these are not completely healthy people with low glucose levels who suddenly, on a statin, become diabetic. What this reinforces is that while there will continue to be a lot of people who require statin treatment, the cornerstone of treatment is lifestyle change: diet, exercise, and weight loss. There is a continuum of risk: Patients at higher risk will benefit from a statin; for patients at very low risk use lifestyle. And if you put a patient on a statin, you need to keep an eye on them."

Dr. Robinson, Dr. Manson, and Dr. Blumenthal said that they had no relevant financial disclosures. Dr. Deedwania said that he has been a consultant to Pfizer, Amarin, and Amgen. Dr. Nicholls said he has received research support from AstraZeneca and has been a consultant to AstraZeneca, Merck, and Pfizer.

The Food and Drug Administration's announcement that the labeling of statins will now note their potential for raising a patient’s blood sugar and glycosylated hemoglobin levels is a reminder that, despite their relative safety, statin treatment poses some level of risk and hence should not be prescribed indiscriminately, experts said.

On the other hand, the risk for blood sugar elevation is modest enough that for the vast majority of patients who have significant cardiovascular disease (CVD) risk, the potential benefit from statin treatment continues to far outweigh the risk patients might face from statin-induced hyperglycemia, according to several experts interviewed for this article. Patients with cardiovascular disease risk who could remain on statins include those who have already had a cardiovascular event, the secondary prevention population, and patients who already have diabetes, considered a coronary risk equivalent because of the sizeable risk that diabetes confers for a future cardiovascular event.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease."

Boosted hyperglycemia that pushes a person’s fasting plasma glucose level to 126 mg/dL or above, the range diagnosed as type 2 diabetes, "is probably the most frequent quantifiable harm from statins" but is still uncommon, noted Dr. Jennifer G. Robinson, professor of medicine and epidemiology at the University of Iowa in Iowa City. She estimated that of the 10%-15% of patients who will develop type 2 diabetes over a period of several years on statin treatment, roughly 1 new case of diabetes out of every 500 incident cases will be attributable to statin treatment, based on the risk information available today.

"It's not very much. It should not change any clinician’s day to day practice in any way," said Dr. Robinson, who is also a vice-chair of the Adult Treatment Panel IV, the group assembled by the National Heart, Lung, and Blood Institute to issue new U.S. cholesterol management guidelines, expected later this year. "It just means that you don’t give a statin to everyone, not someone with a 1% risk for a cardiovascular event over the next 10 years," she said.

Primary prevention poses the most complicated issues, when physicians prescribe statins to people who have not yet had any cardiovascular event. Prescribers face the difficult question of when the risk for incident hyperglycemia triggered by a statin starts to outweigh the benefit from cardiovascular risk reduction. Further muddying the question of whom to exclude from primary prevention with statin treatment are the unknowns that shroud the effect: How do statins cause this? Which patients are most susceptible? Do different statins pose varying levels of hyperglycemia risk?

"As increasingly large populations become candidates for statin treatment, with new guidelines and new methods for CVD risk-prediction modeling, it will be very important to look at the benefit to risk ratio of treatment, including the risk for developing diabetes," said Dr. JoAnn E. Manson, professor of medicine at Harvard Medical School and chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Relatively low-risk groups of patients who are increasingly prescribed statins include adolescents, young adults, and middle-aged women, she noted. "The key is the absolute risk of CVD in these groups, more than their relative risk. In a population with a low absolute risk of CVD events, we need to look very carefully to see where the crossover occurs from net benefit to net risk of treatment."

A problem for the time being is that no good way exists for identifying what factors, beyond borderline high blood glucose at baseline, help identify patients at increased risk for developing diabetes while on statin treatment. Additional research and guidance about what level of fasting plasma glucose at baseline, before a statin regimen starts, should trigger concern, and how often plasma glucose should be monitored once a patient is on a statin, will be helpful, Dr. Manson said.

"Professional societies and expert groups should make clear recommendations about the need for routine vs. targeted glucose testing, as well as the frequency. Consensus guidelines don’t yet exist. The new statin label eliminates testing liver function. Will this be replaced by excessive testing of blood glucose, a practice that could be burdensome to patients and clinicians and drive up health care costs?" she said in an interview.

The dilemma physicians also face when deciding whether to prescribe a statin to patients toward the low end of the cardiovascular risk spectrum is that the same risk factors that might flag patients with a high risk for insulin resistance, hyperglycemia, and the development of type 2 diabetes – factors such as obesity, inadequate physical activity, elements of metabolic syndrome, and a "prediabetic" fasting plasma glucose level of 110-125 mg/dL – also function as cardiovascular disease risk factors.

"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease," Dr. Manson said. She recommended that patients on statin treatment at least be told to be on the alert for developing new symptoms of diabetes: frequent thirst, frequent urination, and blurred vision. "And lifestyle modifications should be intensified to reduce both diabetes and CVD risk."

"The excess risk for diabetes is concentrated in the people with fasting blood sugars in the 115- to 125-mg/dL range" said Dr. Roger S. Blumenthal, professor of medicine and director of preventive medicine at Johns Hopkins Medical Institutions in Baltimore. "A lot of those people are clearly insulin resistant. We almost always have a fasting plasma glucose [when patients are about to start on a statin] as part of a basic lipid profile. With physicians aware of the association, I think this will focus more attention on vulnerable patients in the 115- to 125-mg/dL range, who are headed for diabetes if they don’t make significant improvements in their diet and exercise habits. It’s reasonable to look at glucose and tell patients that a statin might potentially raise their blood sugar by 5-7 mg/dL, but exercising and dropping some excess weight will significantly improve their blood sugar."

Targeted use of plasma glucose testing in statin recipients who seem to have the greatest risk for developing diabetes also received endorsement from Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, in Fresno. He suggested possibly doing annual testing of patients with metabolic syndrome, those who are obese, those with a family history of diabetes, and patients who have previously shown impaired glucose tolerance on a tolerance test.

If a patient’s fasting plasma glucose began to creep up on a statin regimen, "I’d look for other reasons, such as did they gain weight?" he said. Seeing a possible hyperglycemic effect should also prompt a reassessment of whether the patient benefited from the statin, and whether they have made necessary lifestyle changes like improved diet and increased exercise. Rising blood sugar could be used to help motivate a patient to do better on lifestyle measures, and trigger a reevaluation of whether the patient is, on balance, benefiting from the statin, he said. Changing the statin used or the dosage is tricky, because no evidence exists now to support such steps.

But because the biggest signal for the prodiabetic effect of statins came in results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) (N. Engl. J. Med. 2008;359:2195-207), the current perception among at least some physicians is that rosuvastatin (Crestor) poses the biggest hyperglycemic risk. "Some physicians might consider changing [the prescribed statin] from rosuvastatin to simvastatin or atorvastatin," Dr. Blumenthal said.

The FDA took the right step in adding the hyperglycemia information to statin labeling, said Dr. Deedwania. "They give the data, and leave it up to physicians to make their own conclusions."

As a consequence of the FDA’s actions "a lot more physicians will pay attention to glucose as they put patients on statins. The evidence is consistent, and most now agree that it’s real," said Dr. Stephen J. Nicholls, a cardiologist at the Cleveland Clinic. "But these are not completely healthy people with low glucose levels who suddenly, on a statin, become diabetic. What this reinforces is that while there will continue to be a lot of people who require statin treatment, the cornerstone of treatment is lifestyle change: diet, exercise, and weight loss. There is a continuum of risk: Patients at higher risk will benefit from a statin; for patients at very low risk use lifestyle. And if you put a patient on a statin, you need to keep an eye on them."

Dr. Robinson, Dr. Manson, and Dr. Blumenthal said that they had no relevant financial disclosures. Dr. Deedwania said that he has been a consultant to Pfizer, Amarin, and Amgen. Dr. Nicholls said he has received research support from AstraZeneca and has been a consultant to AstraZeneca, Merck, and Pfizer.

Three lots of the antineoplastic drug cytarabine have been recalled because they may not be sterile, according to a posting on the Food and Drug Administration’s MedWatch site.

The nationwide recall applies to lots of cytarabine for injection (1 gm/vial), manufactured by Bedford Laboratories. The risk for lack of sterility was determined from an investigation of the manufacturing area, after the product was released, according to the FDA.

The affected lot numbers are: 2066986, 2111675, and 2131148. Any hospital, physician, clinic, or other health care facility that has any of the affected products should not use it for patients and "should immediately quarantine any product for return," the statement said. Wholesalers, distributors, or retailers that have the recalled product should stop using it and contact the company at 800-562-4797. Click here to report the product to the FDA Medwatch program.

Bedford is one of several generic manufacturers of cytarabine.

Cytarabine is approved for use in combination with other approved cancer treatments for inducing remission of acute nonlymphocytic leukemia in children and adults, and has also been found to be useful in treating acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. It is also indicated in the prophylaxis and treatment of meningeal leukemia, administered intrathecally for this indication.

To view the notice, visit the MedWatch site.

Three lots of the antineoplastic drug cytarabine have been recalled because they may not be sterile, according to a posting on the Food and Drug Administration’s MedWatch site.

The nationwide recall applies to lots of cytarabine for injection (1 gm/vial), manufactured by Bedford Laboratories. The risk for lack of sterility was determined from an investigation of the manufacturing area, after the product was released, according to the FDA.

The affected lot numbers are: 2066986, 2111675, and 2131148. Any hospital, physician, clinic, or other health care facility that has any of the affected products should not use it for patients and "should immediately quarantine any product for return," the statement said. Wholesalers, distributors, or retailers that have the recalled product should stop using it and contact the company at 800-562-4797. Click here to report the product to the FDA Medwatch program.

Bedford is one of several generic manufacturers of cytarabine.

Cytarabine is approved for use in combination with other approved cancer treatments for inducing remission of acute nonlymphocytic leukemia in children and adults, and has also been found to be useful in treating acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. It is also indicated in the prophylaxis and treatment of meningeal leukemia, administered intrathecally for this indication.

To view the notice, visit the MedWatch site.

Three lots of the antineoplastic drug cytarabine have been recalled because they may not be sterile, according to a posting on the Food and Drug Administration’s MedWatch site.

The nationwide recall applies to lots of cytarabine for injection (1 gm/vial), manufactured by Bedford Laboratories. The risk for lack of sterility was determined from an investigation of the manufacturing area, after the product was released, according to the FDA.

The affected lot numbers are: 2066986, 2111675, and 2131148. Any hospital, physician, clinic, or other health care facility that has any of the affected products should not use it for patients and "should immediately quarantine any product for return," the statement said. Wholesalers, distributors, or retailers that have the recalled product should stop using it and contact the company at 800-562-4797. Click here to report the product to the FDA Medwatch program.

Bedford is one of several generic manufacturers of cytarabine.

Cytarabine is approved for use in combination with other approved cancer treatments for inducing remission of acute nonlymphocytic leukemia in children and adults, and has also been found to be useful in treating acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. It is also indicated in the prophylaxis and treatment of meningeal leukemia, administered intrathecally for this indication.

To view the notice, visit the MedWatch site.