Mary Ann Moon

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Worldwide, mortality in adolescents and young adults has overtaken that in children aged 1-4 years, except for a few very-low-income countries, according to a report published online March 29 in the Lancet.

In particular, mortality among young men aged 15-24 years is now two to three times higher than that in young boys, said Russell M. Viner, Ph.D., of the University College London Institute of Child Health and his associates.

This represents a reversal of the historical mortality pattern, and is driven largely by two trends: decreases in both communicable and noncommunicable childhood diseases, and an upsurge in violence- and injury-related deaths in young men. For the first time, children aged 1-4 years now have lower mortality than young men and equivalent mortality to young women, the investigators said.

Mortality among women aged 15-24 years has always been relatively high and continues to be so, because of the excess mortality related to pregnancy and childbirth in this age group.

Research concerning mortality in later childhood, adolescence, and young adulthood has been "neglected," compared with research in infancy and later adulthood, in part because of "the assumption that this period is the healthiest time of life," Dr. Viner and his colleagues said. "However, during the past 50 years, global social, economic, and political changes have adversely affected patterns of health and disease in adolescents and young adults."

The investigators analyzed information in the World Health Organization’s mortality database in what they described as the first international study to examine trends in cause-specific mortality in people aged 1-24 years residing in 50 high-, middle-, low-, and very-low-income countries between 1955 and 2004.

Importantly, because of inaccurate or incomplete data during this period, some very-low-income countries in Africa and Asia could not be included in the study, nor could India and China, the two countries with the largest populations of adolescents and young adults. The study findings therefore cannot be generalized to these countries, the researchers noted.

The study population comprised 436 million young people, representing 15% of the global population in this age group.

In the 1950s, mortality at ages 1-4 years greatly exceeded that of all other age groups in all regions studied. But during the ensuing 50 years, mortality among children aged 1-9 years declined by a dramatic 80%-93%, largely because of a steep decrease in communicable diseases – a decline that was as high as 50-fold in some areas.

Mortality related to noncommunicable juvenile diseases such as asthma, diabetes, and cardiovascular disorders also declined.

Yearly decreases in mortality were large, at approximately 2%, among children aged 5-14 years. In contrast, yearly decreases were much lower, at approximately 0.8%, in males aged 15-24 years. Yearly decreases among young women were intermediate between these two extremes, at approximately 1.5%.

Trends in injury-related deaths also differed greatly between children on the one hand and adolescents combined with young adults on the other. In 2004, injury-related mortality accounted for 25%-36% of all childhood mortality, but for 70%-75% of mortality among males aged 15-24 years. In children, fatal injuries were usually related to transportation, while in adolescents and young men they were often related to violence, increased sensation-seeking behavior, and suicide.

Violence – both interpersonal assault and violence due to larger political upheavals – and suicide became increasingly important causes of death among young men all over the world and among young women in certain regions such as eastern Europe. Overall, violence and suicide now account for up to one-third of mortality in adolescents and young adults in all regions.

"These trends are likely to continue because mortality in children younger than 5 years is expected to decline further, [while] injury-related mortality is expected to increase ... with the continuation of the epidemiological transition in developing countries," according to Dr. Viner and his associates (Lancet 2011 March 29 [doi:10.1016/S0140-6736(11)60106-2]).

Undoubtedly, the inclusion of certain "hot spots" in this study fueled these trends. Eastern European countries showed a clear peak in mortality in the aftermath of the fall of communism, as did some Central and South American countries enmeshed in civil wars.

Pregnancy and childbirth were important causes of mortality in adolescent and young women across the globe in the 1950s, but remain so only in the many low-income countries, and some middle-income countries, today. Such mortality is negligible, accounting for less than 1% of total mortality, in higher-income countries, but it accounts for some 6% of mortality in Central and South American countries.

The study results "support the need for a new focus on the health of adolescents and young adults worldwide. Future global health targets should include the causes of death in people aged 10-24 years, and should extend beyond HIV infection and maternal mortality to include injury and mental health," the investigators said.

There was no funding source for this study. Dr. Viner reported consulting for Esai, and an associate reported receiving travel and living expenses from the World Health Organization.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Pioglitazone reduced the progression from impaired glucose tolerance to type 2 diabetes by 72% in a multicenter study reported in the March 24 issue of the New England Journal of Medicine.

Among 602 adults with impaired glucose tolerance and other risk factors for diabetes, the rate of progressing to diabetes during 2 years of follow-up was 5% in those who took daily oral pioglitazone, compared with 17% in those who took placebo, said Dr. Ralph A. DeFronzo and Dr. Devjit Tripathy of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, and their associates.

However, pioglitazone was associated with significant weight gain and edema, which prompted many subjects to discontinue the drug and drop out of the study, the investigators noted.

They assessed the effect of pioglitazone in men and women (mean age, 52 years) who showed impaired glucose tolerance on an oral glucose-tolerance test, had a body mass index of 25 kg/m² or more, and had at least one other risk factor for diabetes. A total of 407 of the subjects also had elevated fasting glucose levels.

The patients were randomly assigned to receive either oral pioglitazone (303 subjects) or placebo (299 subjects) daily and were followed for a mean of 2.4 years.

Diabetes developed in 50 subjects in the placebo group (17%), compared with only 15 in the pioglitazone group (5%). "The annual average incidence of diabetes, calculated on the basis of person-years, was 7.6% in the placebo group and 2.1% in the pioglitazone group," Dr. DeFronzo and his colleagues wrote (N. Engl. J. Med. 2011;364:1104-15).

"The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year," they added.

At the conclusion of the trial, 48% of the pioglitazone group showed normal glucose tolerance, compared with only 28% of the placebo group.

A total of 161 patients did not complete the trial, including 90 taking pioglitazone and 71 taking placebo. The main reasons for discontinuing were edema and weight gain; edema was more prevalent with the active drug than with placebo.

Pioglitazone’s protective effect was consistent across subgroups of patients regardless of sex, age, weight, race, and fasting glucose level.

Hemoglobin A1c levels remained unchanged in the pioglitazone group throughout the study, but increased in the placebo group. Similarly, diastolic blood pressure was consistently lower in the pioglitazone group.

Body weight, BMI, and body fat increased in both groups, but the gains were greater in the placebo group. Pioglitazone reduced levels of alanine aminotransferase and aspartate aminotransferase. It also increased HDL cholesterol and decreased triglycerides to a greater degree than did placebo.

Previously, concerns have been raised regarding adverse cardiovascular effects in related drugs such as rosiglitazone. In this study, carotid intima-media thickening, a marker of cardiovascular risk, progressed more slowly with pioglitazone than with placebo. This finding, together with lower diastolic blood pressure and higher levels of HDL cholesterol in the pioglitazone group, suggests that the drug "may provide some protection against the development of atherosclerotic cardiovascular disease," the investigators said.

The rates of cardiovascular events were similar, with 26 in the pioglitazone group and 23 in the placebo group. There was one case of heart failure in each group.

Previous studies have reported an increased incidence of fractures with this class of drug. In this study, there were nine fractures in the pioglitazone group and eight in the placebo group, and all the fractures were associated with trauma. The extent to which these benefits affect the long-term complications of diabetes "remains to be determined," the investigators said.

This study was funded by Takeda Pharmaceuticals Inc. Additional support was provided by the General Clinical Research Centers at the University of Tennessee, Knoxville, and the University of Southern California, Los Angeles, and by the Veterans Affairs centers in Phoenix and San Diego. The investigators reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports in the March 24 issue of the New England Journal of Medicine.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European patients who carried the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, while those who did not carry the allele had a probability of 3.8%.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

Hypersensitivity reactions to carbamazepine include maculopapular exanthema (also known as the DRESS syndrome [drug reaction with eosinophilia and systemic symptoms]), the hypersensitivity syndrome, SJS, and TEN.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan. The indications for carbamazepine included epilepsy (14% of subjects), neuralgia (54%), diabetic neuropathy pain (12%), tinnitus (4%), bipolar or other psychiatric disorders (3%), or miscellaneous indications (14%). (Percentages do not equal 100% due to rounding.) Before filling the prescriptions, patients provided blood samples for genotyping and waited 2-3 days for the results.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months for the development of adverse drug reactions.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. SJS is characterized by a rapidly progressive blistering exanthema of macular papules and target-like lesions with mucosal involvement. It has 5% mortality. TEN has a similar presentation but even more extensive detachment of the skin and leads to 25%-35% mortality.

In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

A strong association between the HLA-B*1502 allele and carbamazepine hypersensitivity has been noted before in Han Chinese populations, but more recent research has also demonstrated this connection in Malay, Thai, Indian, and Japanese populations, in which the allele is particularly prevalent. "We speculate that in these countries ... HLA-B*1502 screening could provide a benefit," Dr. Chen and colleagues wrote.

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

"Although the presence of the HLA-A*3101 allele is neither necessary nor sufficient for the development of hypersensitivity to carbamazepine, it is associated with a significantly increased risk," they wrote.

The prevalence of this allele is estimated to be 2%-5% in northern European populations, 2% in Han Chinese populations, and 9% in Japanese populations, they noted.

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Given these calculations, 83 European patients would need to be screened to prevent 1 case of carbamazepine hypersensitivity, while only 56 Japanese patients would need to be screened to prevent 1 case.

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen’s study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen’s associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack’s study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave–the Irish Epilepsy Association, and several other sources. Dr. McCormack’s associates reported ties to numerous industry sources.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.