Jeffrey S. Eisenberg

Patients who are hospitalized with severe sepsis and experience new-onset atrial fibrillation are at increased risk of in-hospital stroke and death, according to a study published online Nov. 13 in JAMA.

New-onset AF develops in an estimated 6%-20% of patients with severe sepsis (that is, sepsis that occurs during the hospital stay rather than existing at admission), according to Dr. Allan J. Walkey of Boston University and colleagues. This suggests that severe sepsis may be a predisposing factor for new AF, they wrote.

They found that in patients with severe sepsis, in-hospital ischemic stroke occurred in 2.6% of those with new-onset AF, compared with 0.57% of those with preexisting AF. It occurred in 0.69% of patients without AF, the researchers found.

This is meaningful because an estimated 60,000 patients with severe sepsis will likely experience new-onset AF in 2011, the authors calculated. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in patients with severe sepsis is as yet uncertain, they wrote (JAMA 2011 Nov. 13 [doi:10.1001/jama.2011.1615]).

The researchers defined new-onset AF as AF or atrial flutter that occurred during the hospital stay but that was not present at the time of admission. They also defined in-hospital ischemic stroke as not being present at the time of admission. They said there had previously been no population-based assessment of the adverse outcomes associated with the new-onset AF that occurs in those patients who have severe sepsis.

"New-onset AF that occurs during severe sepsis is an underrecognized public health problem."

For their retrospective population-based cohort study, the investigators identified 49,082 cases of severe sepsis identified by the ICD-9-CM code 995.92). In-hospital ischemic stroke occurred in a total of 3,310 adult hospitalizations with and without sepsis.

Overall, inpatients with severe sepsis were nearly seven times more likely than those without to have new-onset AF, the investigators found.

And severe sepsis patients with new-onset AF also had a 17% greater risk of in-hospital mortality than did those without new-onset AF (56% vs. 39%, respectively).

"Current guidelines do not address AF that occurs in the setting of severe sepsis or acute infection, suggesting that new-onset AF that occurs during severe sepsis is an underrecognized public health problem. If our findings of increased stroke and death in the setting of AF and severe sepsis are replicated in other data sets, then it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis," they wrote.

Factors that were associated with increased risk of new-onset AF during severe sepsis include demographics (increasing age, male sex, and white race), comorbidities (history of heart failure, obesity, malignancy, and stroke), and various acute factors (such as increasing number of organ failures, respiratory failure, and renal failure).

Potential mechanisms that might explain the increased ischemic stroke risk in patients with severe sepsis and new-onset AF include hemodynamic collapse, increased systemic inflammation, and coagulopathy. Or, new-onset AF "may simply be a market for greater severity of illness and, thus, greater stroke risk," the researchers wrote.

The mean age of patients studied was 69, 48% were women, and the racial/ethnic composition was 56% white, 20% Hispanic, 9% black, and 15% other/missing. The cohort was drawn from the 2007 California State Inpatient Database of 3,144,787 hospitalized adults for all of that year.

This study has several limitations, its authors wrote. The 5.9% incidence of new-onset AF associated with severe sepsis is on the lower end of the 6%-20% reported rates. And clinicians may not report episodes of AF that they consider to be clinically insignificant. Also, an "immortal time" bias may have occurred, meaning that patients had to survive long enough to be diagnosed with AF. Finally, the administrative data used for this study are limited in ascertaining the timing of clinical events.

The study authors reported having no financial conflicts of interest. This study was funded by grants from the Boston University Clinical Translational Research Institute; the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the U.S. Department of Veterans Affairs.

Patients who are hospitalized with severe sepsis and experience new-onset atrial fibrillation are at increased risk of in-hospital stroke and death, according to a study published online Nov. 13 in JAMA.

New-onset AF develops in an estimated 6%-20% of patients with severe sepsis (that is, sepsis that occurs during the hospital stay rather than existing at admission), according to Dr. Allan J. Walkey of Boston University and colleagues. This suggests that severe sepsis may be a predisposing factor for new AF, they wrote.

They found that in patients with severe sepsis, in-hospital ischemic stroke occurred in 2.6% of those with new-onset AF, compared with 0.57% of those with preexisting AF. It occurred in 0.69% of patients without AF, the researchers found.

This is meaningful because an estimated 60,000 patients with severe sepsis will likely experience new-onset AF in 2011, the authors calculated. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in patients with severe sepsis is as yet uncertain, they wrote (JAMA 2011 Nov. 13 [doi:10.1001/jama.2011.1615]).

The researchers defined new-onset AF as AF or atrial flutter that occurred during the hospital stay but that was not present at the time of admission. They also defined in-hospital ischemic stroke as not being present at the time of admission. They said there had previously been no population-based assessment of the adverse outcomes associated with the new-onset AF that occurs in those patients who have severe sepsis.

"New-onset AF that occurs during severe sepsis is an underrecognized public health problem."

For their retrospective population-based cohort study, the investigators identified 49,082 cases of severe sepsis identified by the ICD-9-CM code 995.92). In-hospital ischemic stroke occurred in a total of 3,310 adult hospitalizations with and without sepsis.

Overall, inpatients with severe sepsis were nearly seven times more likely than those without to have new-onset AF, the investigators found.

And severe sepsis patients with new-onset AF also had a 17% greater risk of in-hospital mortality than did those without new-onset AF (56% vs. 39%, respectively).

"Current guidelines do not address AF that occurs in the setting of severe sepsis or acute infection, suggesting that new-onset AF that occurs during severe sepsis is an underrecognized public health problem. If our findings of increased stroke and death in the setting of AF and severe sepsis are replicated in other data sets, then it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis," they wrote.

Factors that were associated with increased risk of new-onset AF during severe sepsis include demographics (increasing age, male sex, and white race), comorbidities (history of heart failure, obesity, malignancy, and stroke), and various acute factors (such as increasing number of organ failures, respiratory failure, and renal failure).

Potential mechanisms that might explain the increased ischemic stroke risk in patients with severe sepsis and new-onset AF include hemodynamic collapse, increased systemic inflammation, and coagulopathy. Or, new-onset AF "may simply be a market for greater severity of illness and, thus, greater stroke risk," the researchers wrote.

The mean age of patients studied was 69, 48% were women, and the racial/ethnic composition was 56% white, 20% Hispanic, 9% black, and 15% other/missing. The cohort was drawn from the 2007 California State Inpatient Database of 3,144,787 hospitalized adults for all of that year.

This study has several limitations, its authors wrote. The 5.9% incidence of new-onset AF associated with severe sepsis is on the lower end of the 6%-20% reported rates. And clinicians may not report episodes of AF that they consider to be clinically insignificant. Also, an "immortal time" bias may have occurred, meaning that patients had to survive long enough to be diagnosed with AF. Finally, the administrative data used for this study are limited in ascertaining the timing of clinical events.

The study authors reported having no financial conflicts of interest. This study was funded by grants from the Boston University Clinical Translational Research Institute; the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the U.S. Department of Veterans Affairs.

Patients who are hospitalized with severe sepsis and experience new-onset atrial fibrillation are at increased risk of in-hospital stroke and death, according to a study published online Nov. 13 in JAMA.

New-onset AF develops in an estimated 6%-20% of patients with severe sepsis (that is, sepsis that occurs during the hospital stay rather than existing at admission), according to Dr. Allan J. Walkey of Boston University and colleagues. This suggests that severe sepsis may be a predisposing factor for new AF, they wrote.

They found that in patients with severe sepsis, in-hospital ischemic stroke occurred in 2.6% of those with new-onset AF, compared with 0.57% of those with preexisting AF. It occurred in 0.69% of patients without AF, the researchers found.

This is meaningful because an estimated 60,000 patients with severe sepsis will likely experience new-onset AF in 2011, the authors calculated. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in patients with severe sepsis is as yet uncertain, they wrote (JAMA 2011 Nov. 13 [doi:10.1001/jama.2011.1615]).

The researchers defined new-onset AF as AF or atrial flutter that occurred during the hospital stay but that was not present at the time of admission. They also defined in-hospital ischemic stroke as not being present at the time of admission. They said there had previously been no population-based assessment of the adverse outcomes associated with the new-onset AF that occurs in those patients who have severe sepsis.

"New-onset AF that occurs during severe sepsis is an underrecognized public health problem."

For their retrospective population-based cohort study, the investigators identified 49,082 cases of severe sepsis identified by the ICD-9-CM code 995.92). In-hospital ischemic stroke occurred in a total of 3,310 adult hospitalizations with and without sepsis.

Overall, inpatients with severe sepsis were nearly seven times more likely than those without to have new-onset AF, the investigators found.

And severe sepsis patients with new-onset AF also had a 17% greater risk of in-hospital mortality than did those without new-onset AF (56% vs. 39%, respectively).

"Current guidelines do not address AF that occurs in the setting of severe sepsis or acute infection, suggesting that new-onset AF that occurs during severe sepsis is an underrecognized public health problem. If our findings of increased stroke and death in the setting of AF and severe sepsis are replicated in other data sets, then it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis," they wrote.

Factors that were associated with increased risk of new-onset AF during severe sepsis include demographics (increasing age, male sex, and white race), comorbidities (history of heart failure, obesity, malignancy, and stroke), and various acute factors (such as increasing number of organ failures, respiratory failure, and renal failure).

Potential mechanisms that might explain the increased ischemic stroke risk in patients with severe sepsis and new-onset AF include hemodynamic collapse, increased systemic inflammation, and coagulopathy. Or, new-onset AF "may simply be a market for greater severity of illness and, thus, greater stroke risk," the researchers wrote.

The mean age of patients studied was 69, 48% were women, and the racial/ethnic composition was 56% white, 20% Hispanic, 9% black, and 15% other/missing. The cohort was drawn from the 2007 California State Inpatient Database of 3,144,787 hospitalized adults for all of that year.

This study has several limitations, its authors wrote. The 5.9% incidence of new-onset AF associated with severe sepsis is on the lower end of the 6%-20% reported rates. And clinicians may not report episodes of AF that they consider to be clinically insignificant. Also, an "immortal time" bias may have occurred, meaning that patients had to survive long enough to be diagnosed with AF. Finally, the administrative data used for this study are limited in ascertaining the timing of clinical events.

The study authors reported having no financial conflicts of interest. This study was funded by grants from the Boston University Clinical Translational Research Institute; the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the U.S. Department of Veterans Affairs.

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.

Infants with high hemoglobin levels who received iron-fortified infant formula had poorer long-term developmental outcomes than those who got a low-iron formula, based on 10-year follow-up data published online Nov. 7 in Archives of Pediatrics & Adolescent Medicine.

Manufacturers routinely fortify infant formula and foods with iron (4-7 mg/L in Europe and 12-13 mg/L in the United States) to reduce the prevalence of iron-deficiency anemia and iron deficiency without anemia. But the optimal amount of iron in such products, especially infant formula, is not known. And the question of whether providing iron to infants whose levels are already sufficient leads to poorer growth, increased morbidity, and effects on the developing brain is also unresolved.

To assess long-term developmental outcomes in children who received iron-fortified formula, Dr. Betsy Lozoff of the University of Michigan, Ann Arbor, and her colleagues conducted a 10-year follow-up of children who participated in a randomized controlled trial in which they received iron-fortified formula or low-iron formula (Arch. Pediatr. Adolesc. Med. 2011 Nov. 7 [doi:10.1001/archpediatrics.2011.197]).

Sarah L.G. Breeden/Elsevier Global Medical News

In the original study (1991-1994), researchers randomized 1,120 healthy, term infants in urban areas around Santiago, Chile, to receive low-iron or iron-fortified formula (2.3 mg/L and 12.7 mg/L) between ages 6 and 12 months; 835 completed the study. At the 10-year follow-up, Dr. Lozoff’s team reassessed 473 children (57% of the original sample). Of these children, 244 had received iron-fortified formula and 229 had received low-iron formula.

The researchers determined that 9 infants (4.1% percent) who received low-iron formula and 17 (6.9%) who got the iron-fortified formula were iron deficient (two or more abnormal iron measures). At 10 years, however, there were no statistically significant differences in iron status between the two groups, and only one child had iron-deficiency anemia.

Dr. Lozoff’s team also measured IQ, spatial memory, arithmetic achievement, visual-motor integration (VMI), visual perception and motor functioning. Scores were similar between both groups at the end of the original randomized controlled trial, but in this study, children who received the higher level of iron-fortified formula scored 1.4-4.6 points lower on every outcome measured. This was statistically significant on the spatial memory and VMI tests.

Another finding: Children who had the highest hemoglobin levels (more than 12.8 g/dL) at age 6 months and received iron-fortified formula scored 10.7-19.3 points lower on these measures than did those with low hemoglobin levels (less than 10.5 g/dL), indicating a poorer long-term developmental outcome. Those with low hemoglobin levels scored 2.6-4.5 points higher.

These findings may be due to the adverse effects of supplemental iron on neurodevelopmental outcome. "This explanation presumes children in our study with high hemoglobin levels in infancy were iron sufficient," Dr. Lozoff and her colleagues said. "However, high hemoglobin levels can be due to other factors, such as chronic hypoxia. Without a panel of iron measures for all infants before randomization, the iron status of those with high hemoglobin levels in our study is uncertain."

"The recommendations of universal iron supplementation might need reconsideration."

Other factors might also be at work, the investigators said. For example, this sample included more female infants and more maternal smoking among infants with high hemoglobin levels. Maternal smoking, in particular, has been associated with poorer developmental outcomes, and hemoglobin levels can be elevated because of chronic mild hypoxia.

Possible limitations to this study include the small number of children (11-13 per formula group, or 5% of the sample) with extremely high hemoglobin levels; high attrition (25% between 6 and 12 months of age and 43% between 12 months and 10 years of age); use of hemoglobin level as the only iron measure for all infants before randomization; and the fact that randomization was not stratified by iron status. In addition, there was a lack of data on maternal smoking at 10 years or smoking habits of other household members at any point; exposure could affect long-term outcome.

More studies are needed, Dr. Lozoff and her colleagues said. Meanwhile, there are several potential implications of these results.

"Hemoglobin levels (and/or other measures of iron status) might need to be tested in early infancy before iron supplementation," the researchers said. "The recommendations of universal iron supplementation might need reconsideration. In any case, the optimal level of iron in infant formula warrants further study to avoid giving more iron than infants need."

Dr. Lozoff and her colleagues said they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.

Infants with high hemoglobin levels who received iron-fortified infant formula had poorer long-term developmental outcomes than those who got a low-iron formula, based on 10-year follow-up data published online Nov. 7 in Archives of Pediatrics & Adolescent Medicine.

Manufacturers routinely fortify infant formula and foods with iron (4-7 mg/L in Europe and 12-13 mg/L in the United States) to reduce the prevalence of iron-deficiency anemia and iron deficiency without anemia. But the optimal amount of iron in such products, especially infant formula, is not known. And the question of whether providing iron to infants whose levels are already sufficient leads to poorer growth, increased morbidity, and effects on the developing brain is also unresolved.

To assess long-term developmental outcomes in children who received iron-fortified formula, Dr. Betsy Lozoff of the University of Michigan, Ann Arbor, and her colleagues conducted a 10-year follow-up of children who participated in a randomized controlled trial in which they received iron-fortified formula or low-iron formula (Arch. Pediatr. Adolesc. Med. 2011 Nov. 7 [doi:10.1001/archpediatrics.2011.197]).

Sarah L.G. Breeden/Elsevier Global Medical News

In the original study (1991-1994), researchers randomized 1,120 healthy, term infants in urban areas around Santiago, Chile, to receive low-iron or iron-fortified formula (2.3 mg/L and 12.7 mg/L) between ages 6 and 12 months; 835 completed the study. At the 10-year follow-up, Dr. Lozoff’s team reassessed 473 children (57% of the original sample). Of these children, 244 had received iron-fortified formula and 229 had received low-iron formula.

The researchers determined that 9 infants (4.1% percent) who received low-iron formula and 17 (6.9%) who got the iron-fortified formula were iron deficient (two or more abnormal iron measures). At 10 years, however, there were no statistically significant differences in iron status between the two groups, and only one child had iron-deficiency anemia.

Dr. Lozoff’s team also measured IQ, spatial memory, arithmetic achievement, visual-motor integration (VMI), visual perception and motor functioning. Scores were similar between both groups at the end of the original randomized controlled trial, but in this study, children who received the higher level of iron-fortified formula scored 1.4-4.6 points lower on every outcome measured. This was statistically significant on the spatial memory and VMI tests.

Another finding: Children who had the highest hemoglobin levels (more than 12.8 g/dL) at age 6 months and received iron-fortified formula scored 10.7-19.3 points lower on these measures than did those with low hemoglobin levels (less than 10.5 g/dL), indicating a poorer long-term developmental outcome. Those with low hemoglobin levels scored 2.6-4.5 points higher.

These findings may be due to the adverse effects of supplemental iron on neurodevelopmental outcome. "This explanation presumes children in our study with high hemoglobin levels in infancy were iron sufficient," Dr. Lozoff and her colleagues said. "However, high hemoglobin levels can be due to other factors, such as chronic hypoxia. Without a panel of iron measures for all infants before randomization, the iron status of those with high hemoglobin levels in our study is uncertain."

"The recommendations of universal iron supplementation might need reconsideration."

Other factors might also be at work, the investigators said. For example, this sample included more female infants and more maternal smoking among infants with high hemoglobin levels. Maternal smoking, in particular, has been associated with poorer developmental outcomes, and hemoglobin levels can be elevated because of chronic mild hypoxia.

Possible limitations to this study include the small number of children (11-13 per formula group, or 5% of the sample) with extremely high hemoglobin levels; high attrition (25% between 6 and 12 months of age and 43% between 12 months and 10 years of age); use of hemoglobin level as the only iron measure for all infants before randomization; and the fact that randomization was not stratified by iron status. In addition, there was a lack of data on maternal smoking at 10 years or smoking habits of other household members at any point; exposure could affect long-term outcome.

More studies are needed, Dr. Lozoff and her colleagues said. Meanwhile, there are several potential implications of these results.

"Hemoglobin levels (and/or other measures of iron status) might need to be tested in early infancy before iron supplementation," the researchers said. "The recommendations of universal iron supplementation might need reconsideration. In any case, the optimal level of iron in infant formula warrants further study to avoid giving more iron than infants need."

Dr. Lozoff and her colleagues said they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.

Infants with high hemoglobin levels who received iron-fortified infant formula had poorer long-term developmental outcomes than those who got a low-iron formula, based on 10-year follow-up data published online Nov. 7 in Archives of Pediatrics & Adolescent Medicine.

Manufacturers routinely fortify infant formula and foods with iron (4-7 mg/L in Europe and 12-13 mg/L in the United States) to reduce the prevalence of iron-deficiency anemia and iron deficiency without anemia. But the optimal amount of iron in such products, especially infant formula, is not known. And the question of whether providing iron to infants whose levels are already sufficient leads to poorer growth, increased morbidity, and effects on the developing brain is also unresolved.

To assess long-term developmental outcomes in children who received iron-fortified formula, Dr. Betsy Lozoff of the University of Michigan, Ann Arbor, and her colleagues conducted a 10-year follow-up of children who participated in a randomized controlled trial in which they received iron-fortified formula or low-iron formula (Arch. Pediatr. Adolesc. Med. 2011 Nov. 7 [doi:10.1001/archpediatrics.2011.197]).

Sarah L.G. Breeden/Elsevier Global Medical News

In the original study (1991-1994), researchers randomized 1,120 healthy, term infants in urban areas around Santiago, Chile, to receive low-iron or iron-fortified formula (2.3 mg/L and 12.7 mg/L) between ages 6 and 12 months; 835 completed the study. At the 10-year follow-up, Dr. Lozoff’s team reassessed 473 children (57% of the original sample). Of these children, 244 had received iron-fortified formula and 229 had received low-iron formula.

The researchers determined that 9 infants (4.1% percent) who received low-iron formula and 17 (6.9%) who got the iron-fortified formula were iron deficient (two or more abnormal iron measures). At 10 years, however, there were no statistically significant differences in iron status between the two groups, and only one child had iron-deficiency anemia.

Dr. Lozoff’s team also measured IQ, spatial memory, arithmetic achievement, visual-motor integration (VMI), visual perception and motor functioning. Scores were similar between both groups at the end of the original randomized controlled trial, but in this study, children who received the higher level of iron-fortified formula scored 1.4-4.6 points lower on every outcome measured. This was statistically significant on the spatial memory and VMI tests.

Another finding: Children who had the highest hemoglobin levels (more than 12.8 g/dL) at age 6 months and received iron-fortified formula scored 10.7-19.3 points lower on these measures than did those with low hemoglobin levels (less than 10.5 g/dL), indicating a poorer long-term developmental outcome. Those with low hemoglobin levels scored 2.6-4.5 points higher.

These findings may be due to the adverse effects of supplemental iron on neurodevelopmental outcome. "This explanation presumes children in our study with high hemoglobin levels in infancy were iron sufficient," Dr. Lozoff and her colleagues said. "However, high hemoglobin levels can be due to other factors, such as chronic hypoxia. Without a panel of iron measures for all infants before randomization, the iron status of those with high hemoglobin levels in our study is uncertain."

"The recommendations of universal iron supplementation might need reconsideration."

Other factors might also be at work, the investigators said. For example, this sample included more female infants and more maternal smoking among infants with high hemoglobin levels. Maternal smoking, in particular, has been associated with poorer developmental outcomes, and hemoglobin levels can be elevated because of chronic mild hypoxia.

Possible limitations to this study include the small number of children (11-13 per formula group, or 5% of the sample) with extremely high hemoglobin levels; high attrition (25% between 6 and 12 months of age and 43% between 12 months and 10 years of age); use of hemoglobin level as the only iron measure for all infants before randomization; and the fact that randomization was not stratified by iron status. In addition, there was a lack of data on maternal smoking at 10 years or smoking habits of other household members at any point; exposure could affect long-term outcome.

More studies are needed, Dr. Lozoff and her colleagues said. Meanwhile, there are several potential implications of these results.

"Hemoglobin levels (and/or other measures of iron status) might need to be tested in early infancy before iron supplementation," the researchers said. "The recommendations of universal iron supplementation might need reconsideration. In any case, the optimal level of iron in infant formula warrants further study to avoid giving more iron than infants need."

Dr. Lozoff and her colleagues said they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to Nov. 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

The researchers obtained information annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient's next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information “might affect the decision to taper or continue antiepileptic drugs,” the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of “over-optimistic expectations” implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including “the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients.”

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

View on the News

Epilepsy Surgery Validated, but New Questions Raised

This study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy. It also is unlike other epilepsy surgery studies in that it prospectively analyzed seizure freedom at successive annual visits in individual patients instead of only at the last follow-up visit.

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and resection strategies to optimize long-term seizure control.

 Dr. Ahmed-Ramadan Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor William Peter Gray of University of Southampton wrote their comments in an editorial accompanying the epilepsy surgery study (Lancet 2011;378:1360-2). They reported having no conflicts of interest.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to Nov. 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

The researchers obtained information annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient's next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information “might affect the decision to taper or continue antiepileptic drugs,” the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of “over-optimistic expectations” implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including “the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients.”

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

View on the News

Epilepsy Surgery Validated, but New Questions Raised

This study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy. It also is unlike other epilepsy surgery studies in that it prospectively analyzed seizure freedom at successive annual visits in individual patients instead of only at the last follow-up visit.

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and resection strategies to optimize long-term seizure control.

 Dr. Ahmed-Ramadan Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor William Peter Gray of University of Southampton wrote their comments in an editorial accompanying the epilepsy surgery study (Lancet 2011;378:1360-2). They reported having no conflicts of interest.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to Nov. 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

The researchers obtained information annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient's next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information “might affect the decision to taper or continue antiepileptic drugs,” the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of “over-optimistic expectations” implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including “the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients.”

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

View on the News

Epilepsy Surgery Validated, but New Questions Raised

This study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy. It also is unlike other epilepsy surgery studies in that it prospectively analyzed seizure freedom at successive annual visits in individual patients instead of only at the last follow-up visit.

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and resection strategies to optimize long-term seizure control.

 Dr. Ahmed-Ramadan Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor William Peter Gray of University of Southampton wrote their comments in an editorial accompanying the epilepsy surgery study (Lancet 2011;378:1360-2). They reported having no conflicts of interest.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

BALTIMORE – Young children with melanoma are more likely to have sentinel lymph node metastases than older children and young adults, according to the results of a new study.

The study also found that thickness and ulceration were strong predictors of sentinel lymph node biopsy (SLNB) in children and young adults with melanoma (Cancer 2011 Oct. 5 [doi:10.1002/cncr.26578]).

Using the 2008 Surveillance, Epidemiology, and End Results (SEER) databases, Euphemia Mu, of Johns Hopkins University, Baltimore, and colleagues analyzed the medical records of 717 children (79 were aged less than 10 years and 638 were aged 10-19) and 1,368 young adults (aged 20-24) who were diagnosed with melanoma between 2003 and 2008.

The researchers gathered demographic and tumor data, and compared tests results from lymph node biopsies based on tumor size, tumor appearance, and age. Median follow-up for all patients was 34 months. Results offered information about:

• Demographics. Younger children with melanoma were more often male (47%) and nonwhite (9%), compared with adolescents (41% male, 2% nonwhite) and young adults (31% male, 1.4% nonwhite).

• Presentation. Melanoma in young children more frequently presented with distant metastases (6%), nodular morphology (10%), and more than 1 mm thickness (40%), compared with tumors in adolescents (1% metastatic, 5% nodular, and 28% more than 1 mm thick) and young adults (2% metastatic, 6% nodular, and 22% with thickness of 1 mm or higher). The proportion with ulceration did not differ significantly among these age groups.

• Likelihood of biopsy. In all, 40% of children and 31% of young adults who had localized disease on examination underwent SLN biopsy. Of those who met the recommendations for SLN biopsy (more than 1 mm in thickness or ulceration), 74% of children and 70% of young adults underwent SLN biopsy. In pediatric and young adult patients, ulceration, histology, thickness, sex, and primary site were correlated significantly with undergoing SLN biopsy.

• Metastases. A total of 25% of children and 14% of young adults who underwent biopsy had SLN metastases. Children whose melanomas were between 1.01 mm and 2.00 mm thick had SLN metastases more often than young adults (24% vs. 4%).

"This finding supports the idea that some melanomas in children may differ biologically from melanomas in adults and should encourage future efforts to investigate the biologic heterogeneity of melanoma," the researchers wrote.

Other characteristics associated with SLN metastases in patients included ulceration (62%) and nodular histology (43%). Overall, children were more likely than young adults to have SLN metastases for all analyzed characteristics (ulceration, histology, thickness, sex, and primary site).

• Prognosis. There was no statistically significant difference in survival between adults and children who tested positive on SLN biopsy. Four out of 64 children (6.3%) and 4 out of 54 young adults (7.4%) who tested positive died vs. 1 of 182 children (0.5%) and 3 of 322 young adults (0.9%) who tested negative.

• Completion lymph node dissection (CLND). Among patients who had negative SLN biopsies, 16% of pediatric and 12% of adult patients underwent CLND, compared with 78% of pediatric patients and 73% of young adult patients who had positive biopsies.

Findings of this study are "a powerful reminder that there’s much about pediatric melanoma that we don’t understand and that, just as is the case with other diseases, children are not small adults, but differ markedly in their response to disease," senior investigator Dr. John J. Strouse, a pediatric hematologist and oncologist at Johns Hopkins, said in a statement.

Study limitations included lack of a centralized review of diagnostic specimens, absence of information regarding mitotic rate, and lack of information about socioeconomic factors, the investigators noted.

Although this study was an important comparison for understanding age-related differences in melanoma characteristics, studies are needed that compare SLN biopsy use and results in pediatric cases with adult cases.

The study investigators made no disclosures.

BALTIMORE – Young children with melanoma are more likely to have sentinel lymph node metastases than older children and young adults, according to the results of a new study.

The study also found that thickness and ulceration were strong predictors of sentinel lymph node biopsy (SLNB) in children and young adults with melanoma (Cancer 2011 Oct. 5 [doi:10.1002/cncr.26578]).

Using the 2008 Surveillance, Epidemiology, and End Results (SEER) databases, Euphemia Mu, of Johns Hopkins University, Baltimore, and colleagues analyzed the medical records of 717 children (79 were aged less than 10 years and 638 were aged 10-19) and 1,368 young adults (aged 20-24) who were diagnosed with melanoma between 2003 and 2008.

The researchers gathered demographic and tumor data, and compared tests results from lymph node biopsies based on tumor size, tumor appearance, and age. Median follow-up for all patients was 34 months. Results offered information about:

• Demographics. Younger children with melanoma were more often male (47%) and nonwhite (9%), compared with adolescents (41% male, 2% nonwhite) and young adults (31% male, 1.4% nonwhite).

• Presentation. Melanoma in young children more frequently presented with distant metastases (6%), nodular morphology (10%), and more than 1 mm thickness (40%), compared with tumors in adolescents (1% metastatic, 5% nodular, and 28% more than 1 mm thick) and young adults (2% metastatic, 6% nodular, and 22% with thickness of 1 mm or higher). The proportion with ulceration did not differ significantly among these age groups.

• Likelihood of biopsy. In all, 40% of children and 31% of young adults who had localized disease on examination underwent SLN biopsy. Of those who met the recommendations for SLN biopsy (more than 1 mm in thickness or ulceration), 74% of children and 70% of young adults underwent SLN biopsy. In pediatric and young adult patients, ulceration, histology, thickness, sex, and primary site were correlated significantly with undergoing SLN biopsy.

• Metastases. A total of 25% of children and 14% of young adults who underwent biopsy had SLN metastases. Children whose melanomas were between 1.01 mm and 2.00 mm thick had SLN metastases more often than young adults (24% vs. 4%).

"This finding supports the idea that some melanomas in children may differ biologically from melanomas in adults and should encourage future efforts to investigate the biologic heterogeneity of melanoma," the researchers wrote.

Other characteristics associated with SLN metastases in patients included ulceration (62%) and nodular histology (43%). Overall, children were more likely than young adults to have SLN metastases for all analyzed characteristics (ulceration, histology, thickness, sex, and primary site).

• Prognosis. There was no statistically significant difference in survival between adults and children who tested positive on SLN biopsy. Four out of 64 children (6.3%) and 4 out of 54 young adults (7.4%) who tested positive died vs. 1 of 182 children (0.5%) and 3 of 322 young adults (0.9%) who tested negative.

• Completion lymph node dissection (CLND). Among patients who had negative SLN biopsies, 16% of pediatric and 12% of adult patients underwent CLND, compared with 78% of pediatric patients and 73% of young adult patients who had positive biopsies.

Findings of this study are "a powerful reminder that there’s much about pediatric melanoma that we don’t understand and that, just as is the case with other diseases, children are not small adults, but differ markedly in their response to disease," senior investigator Dr. John J. Strouse, a pediatric hematologist and oncologist at Johns Hopkins, said in a statement.

Study limitations included lack of a centralized review of diagnostic specimens, absence of information regarding mitotic rate, and lack of information about socioeconomic factors, the investigators noted.

Although this study was an important comparison for understanding age-related differences in melanoma characteristics, studies are needed that compare SLN biopsy use and results in pediatric cases with adult cases.

The study investigators made no disclosures.

BALTIMORE – Young children with melanoma are more likely to have sentinel lymph node metastases than older children and young adults, according to the results of a new study.

The study also found that thickness and ulceration were strong predictors of sentinel lymph node biopsy (SLNB) in children and young adults with melanoma (Cancer 2011 Oct. 5 [doi:10.1002/cncr.26578]).

Using the 2008 Surveillance, Epidemiology, and End Results (SEER) databases, Euphemia Mu, of Johns Hopkins University, Baltimore, and colleagues analyzed the medical records of 717 children (79 were aged less than 10 years and 638 were aged 10-19) and 1,368 young adults (aged 20-24) who were diagnosed with melanoma between 2003 and 2008.

The researchers gathered demographic and tumor data, and compared tests results from lymph node biopsies based on tumor size, tumor appearance, and age. Median follow-up for all patients was 34 months. Results offered information about:

• Demographics. Younger children with melanoma were more often male (47%) and nonwhite (9%), compared with adolescents (41% male, 2% nonwhite) and young adults (31% male, 1.4% nonwhite).

• Presentation. Melanoma in young children more frequently presented with distant metastases (6%), nodular morphology (10%), and more than 1 mm thickness (40%), compared with tumors in adolescents (1% metastatic, 5% nodular, and 28% more than 1 mm thick) and young adults (2% metastatic, 6% nodular, and 22% with thickness of 1 mm or higher). The proportion with ulceration did not differ significantly among these age groups.

• Likelihood of biopsy. In all, 40% of children and 31% of young adults who had localized disease on examination underwent SLN biopsy. Of those who met the recommendations for SLN biopsy (more than 1 mm in thickness or ulceration), 74% of children and 70% of young adults underwent SLN biopsy. In pediatric and young adult patients, ulceration, histology, thickness, sex, and primary site were correlated significantly with undergoing SLN biopsy.

• Metastases. A total of 25% of children and 14% of young adults who underwent biopsy had SLN metastases. Children whose melanomas were between 1.01 mm and 2.00 mm thick had SLN metastases more often than young adults (24% vs. 4%).

"This finding supports the idea that some melanomas in children may differ biologically from melanomas in adults and should encourage future efforts to investigate the biologic heterogeneity of melanoma," the researchers wrote.

Other characteristics associated with SLN metastases in patients included ulceration (62%) and nodular histology (43%). Overall, children were more likely than young adults to have SLN metastases for all analyzed characteristics (ulceration, histology, thickness, sex, and primary site).

• Prognosis. There was no statistically significant difference in survival between adults and children who tested positive on SLN biopsy. Four out of 64 children (6.3%) and 4 out of 54 young adults (7.4%) who tested positive died vs. 1 of 182 children (0.5%) and 3 of 322 young adults (0.9%) who tested negative.

• Completion lymph node dissection (CLND). Among patients who had negative SLN biopsies, 16% of pediatric and 12% of adult patients underwent CLND, compared with 78% of pediatric patients and 73% of young adult patients who had positive biopsies.

Findings of this study are "a powerful reminder that there’s much about pediatric melanoma that we don’t understand and that, just as is the case with other diseases, children are not small adults, but differ markedly in their response to disease," senior investigator Dr. John J. Strouse, a pediatric hematologist and oncologist at Johns Hopkins, said in a statement.

Study limitations included lack of a centralized review of diagnostic specimens, absence of information regarding mitotic rate, and lack of information about socioeconomic factors, the investigators noted.

Although this study was an important comparison for understanding age-related differences in melanoma characteristics, studies are needed that compare SLN biopsy use and results in pediatric cases with adult cases.

The study investigators made no disclosures.

Despite a 24% increase in the decade between 1999 and 2009, hospitalizations for a principal or secondary diagnosis of an eating disorder have declined in recent years, according to a statistical brief from the Healthcare Cost and Utilization Project. The one exception is pica, in which the number of cases nearly doubled during this period.

HCUP, sponsored by the Agency for Healthcare Research and Quality (AHRQ), combines the data of private and government organizations to create a national information resource. In this statistical brief, Yafu Zhao, MS, and William Encinosa, Ph.D., present data on national estimates of hospitalizations for eating disorders during the decade between 1999-2000 and 2008-2009 (HCUP Statistical Brief #120, September 2011). A previous statistical brief looked at hospitalizations for eating disorders between 1999 and 2006, but not much is known about recent trends, the authors say.

The quality of outpatient care for eating disorders may have improved significantly, particularly between 2007 and 2009, to reduce principal diagnosis eating disorder hospitalizations.

Eating disorders, especially anorexia nervosa, have the highest mortality rate of any psychiatric disorders. Patients often require hospitalization to treat secondary disorders, such as severe starvation, cardiac arrhythmia, severe dehydration, gastrointestinal problems, depression, fluid and electrolyte disorders, schizophrenia, or alcohol-related disorders.

In comparing the data between 1999-2000 and 2008-2009, the numbers look bleak. Specifically, 29,533 individuals were hospitalized for an eating disorder in 2008-2009, up 24% from 23,807 in 1999-2000, according to HCUP. Hospitalizations with eating disorder as the principal diagnosis actually declined by 1% during the decade, from 5,689 to 5,587, but hospitalizations with eating disorder as a secondary diagnosis increased 40%, from 17,118 to 23,946.

Between 1999-2000 and 2000-2009, there were significant increases in serious complications in patients with eating disorders. This includes nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, which increased by 129%; acute renal or liver failure, 127%; cardiac dysrhythmias, 103%; menstrual disorders, 62%; deficiency and other anemia, 66%; convulsions/epilepsy, 55%; and fluid and electrolyte disorders, 18%.

Also noteworthy: Hospitalizations for pica, in which patients eat inedible materials such as soil or feces, increased by 93%, Some 31% percent of children who were hospitalized with pica in 2009 had an autism spectrum disorder.

However, a comparison of numbers between 2007-2008 and 2008-2009 offers a better outlook: Hospitalizations declined 4%, from 30,754 cases to 29,533, during this time. Eating disorder as a principal diagnosis declined 23%, from 7,290 cases to 5,587. The number of hospitalizations with eating disorder as a secondary cause did increase slightly, by 482 cases

Between 2007-2008 and 2008-2009, however, there were decreases in serious complications, namely nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, 12%; acute renal or liver failure, 39%; cardiac dysrhythmias, 39%; menstrual disorders, 46%; deficiency and other anemia, 27%; convulsions/epilepsy, 17%; and fluid and electrolyte disorders, 23%. One exception: Hospitalizations for pica increased 5% between 2007-2008 and 2008-2009.

"Overall, the results of this Statistical Brief indicate that the quality of outpatient care for eating disorders may have improved significantly between 1999 and 2009, particularly between 2007 and 2009, in such a way as to reduce principal diagnosis eating disorder hospitalizations," the authors say. "It is doubtful that this is an artifact of the 2009 recession, since secondary diagnosis eating disorder hospitalizations did not decline during the recession."

The HCUP data also provides some demographic data about patients with eating disorders. Specifically, 9 out of 10 patients who have eating disorders are women, eating disorders increased by 53% in men vs. 21% of women between 1999-2000 and 2008-2009 vs. 21% in women.

In 2008-2009, 3% percent of hospital stays involving eating disorders were for children younger than 12. Additional eating-disorder patient stays by age are as follows: 12 to 19 years, 19% of stays; 19 to 30, 28%; 30 to 45, 25%; 45 to 64, 18%; and 65 and older, 7%.

The aggregate costs for any hospital stay involving eating disorders was $277 million, up 68% from $165 million in 1999-2000. The average cost per hospital stay went from $7,300 in 1999-2000 to $9,400 in 2008-2009, a 28.8% increase. The average length of hospital stay was unchanged at 8 days.

The authors reported having no disclosures.

Despite a 24% increase in the decade between 1999 and 2009, hospitalizations for a principal or secondary diagnosis of an eating disorder have declined in recent years, according to a statistical brief from the Healthcare Cost and Utilization Project. The one exception is pica, in which the number of cases nearly doubled during this period.

HCUP, sponsored by the Agency for Healthcare Research and Quality (AHRQ), combines the data of private and government organizations to create a national information resource. In this statistical brief, Yafu Zhao, MS, and William Encinosa, Ph.D., present data on national estimates of hospitalizations for eating disorders during the decade between 1999-2000 and 2008-2009 (HCUP Statistical Brief #120, September 2011). A previous statistical brief looked at hospitalizations for eating disorders between 1999 and 2006, but not much is known about recent trends, the authors say.

The quality of outpatient care for eating disorders may have improved significantly, particularly between 2007 and 2009, to reduce principal diagnosis eating disorder hospitalizations.

Eating disorders, especially anorexia nervosa, have the highest mortality rate of any psychiatric disorders. Patients often require hospitalization to treat secondary disorders, such as severe starvation, cardiac arrhythmia, severe dehydration, gastrointestinal problems, depression, fluid and electrolyte disorders, schizophrenia, or alcohol-related disorders.

In comparing the data between 1999-2000 and 2008-2009, the numbers look bleak. Specifically, 29,533 individuals were hospitalized for an eating disorder in 2008-2009, up 24% from 23,807 in 1999-2000, according to HCUP. Hospitalizations with eating disorder as the principal diagnosis actually declined by 1% during the decade, from 5,689 to 5,587, but hospitalizations with eating disorder as a secondary diagnosis increased 40%, from 17,118 to 23,946.

Between 1999-2000 and 2000-2009, there were significant increases in serious complications in patients with eating disorders. This includes nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, which increased by 129%; acute renal or liver failure, 127%; cardiac dysrhythmias, 103%; menstrual disorders, 62%; deficiency and other anemia, 66%; convulsions/epilepsy, 55%; and fluid and electrolyte disorders, 18%.

Also noteworthy: Hospitalizations for pica, in which patients eat inedible materials such as soil or feces, increased by 93%, Some 31% percent of children who were hospitalized with pica in 2009 had an autism spectrum disorder.

However, a comparison of numbers between 2007-2008 and 2008-2009 offers a better outlook: Hospitalizations declined 4%, from 30,754 cases to 29,533, during this time. Eating disorder as a principal diagnosis declined 23%, from 7,290 cases to 5,587. The number of hospitalizations with eating disorder as a secondary cause did increase slightly, by 482 cases

Between 2007-2008 and 2008-2009, however, there were decreases in serious complications, namely nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, 12%; acute renal or liver failure, 39%; cardiac dysrhythmias, 39%; menstrual disorders, 46%; deficiency and other anemia, 27%; convulsions/epilepsy, 17%; and fluid and electrolyte disorders, 23%. One exception: Hospitalizations for pica increased 5% between 2007-2008 and 2008-2009.

"Overall, the results of this Statistical Brief indicate that the quality of outpatient care for eating disorders may have improved significantly between 1999 and 2009, particularly between 2007 and 2009, in such a way as to reduce principal diagnosis eating disorder hospitalizations," the authors say. "It is doubtful that this is an artifact of the 2009 recession, since secondary diagnosis eating disorder hospitalizations did not decline during the recession."

The HCUP data also provides some demographic data about patients with eating disorders. Specifically, 9 out of 10 patients who have eating disorders are women, eating disorders increased by 53% in men vs. 21% of women between 1999-2000 and 2008-2009 vs. 21% in women.

In 2008-2009, 3% percent of hospital stays involving eating disorders were for children younger than 12. Additional eating-disorder patient stays by age are as follows: 12 to 19 years, 19% of stays; 19 to 30, 28%; 30 to 45, 25%; 45 to 64, 18%; and 65 and older, 7%.

The aggregate costs for any hospital stay involving eating disorders was $277 million, up 68% from $165 million in 1999-2000. The average cost per hospital stay went from $7,300 in 1999-2000 to $9,400 in 2008-2009, a 28.8% increase. The average length of hospital stay was unchanged at 8 days.

The authors reported having no disclosures.

Despite a 24% increase in the decade between 1999 and 2009, hospitalizations for a principal or secondary diagnosis of an eating disorder have declined in recent years, according to a statistical brief from the Healthcare Cost and Utilization Project. The one exception is pica, in which the number of cases nearly doubled during this period.

HCUP, sponsored by the Agency for Healthcare Research and Quality (AHRQ), combines the data of private and government organizations to create a national information resource. In this statistical brief, Yafu Zhao, MS, and William Encinosa, Ph.D., present data on national estimates of hospitalizations for eating disorders during the decade between 1999-2000 and 2008-2009 (HCUP Statistical Brief #120, September 2011). A previous statistical brief looked at hospitalizations for eating disorders between 1999 and 2006, but not much is known about recent trends, the authors say.

The quality of outpatient care for eating disorders may have improved significantly, particularly between 2007 and 2009, to reduce principal diagnosis eating disorder hospitalizations.

Eating disorders, especially anorexia nervosa, have the highest mortality rate of any psychiatric disorders. Patients often require hospitalization to treat secondary disorders, such as severe starvation, cardiac arrhythmia, severe dehydration, gastrointestinal problems, depression, fluid and electrolyte disorders, schizophrenia, or alcohol-related disorders.

In comparing the data between 1999-2000 and 2008-2009, the numbers look bleak. Specifically, 29,533 individuals were hospitalized for an eating disorder in 2008-2009, up 24% from 23,807 in 1999-2000, according to HCUP. Hospitalizations with eating disorder as the principal diagnosis actually declined by 1% during the decade, from 5,689 to 5,587, but hospitalizations with eating disorder as a secondary diagnosis increased 40%, from 17,118 to 23,946.

Between 1999-2000 and 2000-2009, there were significant increases in serious complications in patients with eating disorders. This includes nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, which increased by 129%; acute renal or liver failure, 127%; cardiac dysrhythmias, 103%; menstrual disorders, 62%; deficiency and other anemia, 66%; convulsions/epilepsy, 55%; and fluid and electrolyte disorders, 18%.

Also noteworthy: Hospitalizations for pica, in which patients eat inedible materials such as soil or feces, increased by 93%, Some 31% percent of children who were hospitalized with pica in 2009 had an autism spectrum disorder.

However, a comparison of numbers between 2007-2008 and 2008-2009 offers a better outlook: Hospitalizations declined 4%, from 30,754 cases to 29,533, during this time. Eating disorder as a principal diagnosis declined 23%, from 7,290 cases to 5,587. The number of hospitalizations with eating disorder as a secondary cause did increase slightly, by 482 cases

Between 2007-2008 and 2008-2009, however, there were decreases in serious complications, namely nutritional deficiencies and other nutritional, endocrine, and metabolic disorders, 12%; acute renal or liver failure, 39%; cardiac dysrhythmias, 39%; menstrual disorders, 46%; deficiency and other anemia, 27%; convulsions/epilepsy, 17%; and fluid and electrolyte disorders, 23%. One exception: Hospitalizations for pica increased 5% between 2007-2008 and 2008-2009.

"Overall, the results of this Statistical Brief indicate that the quality of outpatient care for eating disorders may have improved significantly between 1999 and 2009, particularly between 2007 and 2009, in such a way as to reduce principal diagnosis eating disorder hospitalizations," the authors say. "It is doubtful that this is an artifact of the 2009 recession, since secondary diagnosis eating disorder hospitalizations did not decline during the recession."

The HCUP data also provides some demographic data about patients with eating disorders. Specifically, 9 out of 10 patients who have eating disorders are women, eating disorders increased by 53% in men vs. 21% of women between 1999-2000 and 2008-2009 vs. 21% in women.

In 2008-2009, 3% percent of hospital stays involving eating disorders were for children younger than 12. Additional eating-disorder patient stays by age are as follows: 12 to 19 years, 19% of stays; 19 to 30, 28%; 30 to 45, 25%; 45 to 64, 18%; and 65 and older, 7%.

The aggregate costs for any hospital stay involving eating disorders was $277 million, up 68% from $165 million in 1999-2000. The average cost per hospital stay went from $7,300 in 1999-2000 to $9,400 in 2008-2009, a 28.8% increase. The average length of hospital stay was unchanged at 8 days.

The authors reported having no disclosures.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study reported in the Oct. 15 issue of the Lancet.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to November 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

Information was obtained annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient’s next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information "might affect the decision to taper or continue antiepileptic drugs," the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of "over-optimistic expectations" implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including "the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients."

In an editorial accompanying the epilepsy surgery study, Dr. Ahmed-Ramadan Sadek and Professor William Peter Gray wrote that this study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy (Lancet 2011;378:1360-2).

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients said Dr. Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor Gray of University of Southampton.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and reselection strategies to optimize long-term seizure control.

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

Dr. Sadek and Professor Gray reported having no conflicts of interest.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study reported in the Oct. 15 issue of the Lancet.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to November 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

Information was obtained annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient’s next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information "might affect the decision to taper or continue antiepileptic drugs," the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of "over-optimistic expectations" implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including "the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients."

In an editorial accompanying the epilepsy surgery study, Dr. Ahmed-Ramadan Sadek and Professor William Peter Gray wrote that this study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy (Lancet 2011;378:1360-2).

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients said Dr. Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor Gray of University of Southampton.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and reselection strategies to optimize long-term seizure control.

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

Dr. Sadek and Professor Gray reported having no conflicts of interest.

Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study reported in the Oct. 15 issue of the Lancet.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to November 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

Information was obtained annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient’s next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information "might affect the decision to taper or continue antiepileptic drugs," the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of "over-optimistic expectations" implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including "the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients."

In an editorial accompanying the epilepsy surgery study, Dr. Ahmed-Ramadan Sadek and Professor William Peter Gray wrote that this study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy (Lancet 2011;378:1360-2).

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients said Dr. Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor Gray of University of Southampton.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and reselection strategies to optimize long-term seizure control.

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

Dr. Sadek and Professor Gray reported having no conflicts of interest.

Major Finding: Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60–64 who are not yet eligible for Medicare but are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. Studies of this and similar programs show that participants ages 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals aged 60–64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would see net savings of $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such as how broad eligibility and participation are, the researchers said. They used a 4.2% weight loss impact to avoid overestimation, so the program might have larger effects than expected.

Major Finding: Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60–64 who are not yet eligible for Medicare but are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. Studies of this and similar programs show that participants ages 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals aged 60–64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would see net savings of $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such as how broad eligibility and participation are, the researchers said. They used a 4.2% weight loss impact to avoid overestimation, so the program might have larger effects than expected.

Major Finding: Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60–64 who are not yet eligible for Medicare but are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. Studies of this and similar programs show that participants ages 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals aged 60–64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would see net savings of $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such as how broad eligibility and participation are, the researchers said. They used a 4.2% weight loss impact to avoid overestimation, so the program might have larger effects than expected.

Major Finding: Community-based weight loss programs for individuals aged 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Medicare could be in the position to save between $7 billion and $15 billion over the remaining lifetimes of one cohort of baby boomers if community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease were to be instituted, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60-64 who are not yet eligible for Medicare but who are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. The program is provided by 50 YMCAs and is available at more than 116 sites in 24 states. Studies of this and similar programs show that participants aged 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals ages 60-64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would save $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

“Our results show the potential savings to Medicare if a proven community-based approach to reducing obesity and related chronic disease were to be made available, nationwide, to high-risk individuals soon to become Medicare beneficiaries,” the researchers said. “In doing so, they also present a potential business case for the federal government to partner with the private sector in order to encourage broad enrollment in effective weight loss programs.”Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such eligibility and participation, they said.

Major Finding: Community-based weight loss programs for individuals aged 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Medicare could be in the position to save between $7 billion and $15 billion over the remaining lifetimes of one cohort of baby boomers if community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease were to be instituted, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60-64 who are not yet eligible for Medicare but who are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. The program is provided by 50 YMCAs and is available at more than 116 sites in 24 states. Studies of this and similar programs show that participants aged 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals ages 60-64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would save $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

“Our results show the potential savings to Medicare if a proven community-based approach to reducing obesity and related chronic disease were to be made available, nationwide, to high-risk individuals soon to become Medicare beneficiaries,” the researchers said. “In doing so, they also present a potential business case for the federal government to partner with the private sector in order to encourage broad enrollment in effective weight loss programs.”Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such eligibility and participation, they said.

Major Finding: Community-based weight loss programs for individuals aged 60 years or older who are at risk for diabetes or heart disease could save Medicare between $7 billion and $15 billion over the lifetimes of one cohort of baby boomers.

Data Source: Estimates of net savings to Medicare over 10 years and participants' lifetimes.

Disclosures: The authors had no financial disclosures. The Peter G. Peterson Foundation provided assistance for carrying out the research.

ATLANTA – Medicare could be in the position to save between $7 billion and $15 billion over the remaining lifetimes of one cohort of baby boomers if community-based weight loss programs for individuals ages 60 years or older who are at risk for diabetes or heart disease were to be instituted, according to a recent study.

Obesity, defined as body mass index (BMI) of 30 kg/m

“It seems to me that Medicare has an incentive to reach out earlier and improve the health of people who will be coming into the program,” study author, Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, said in a statement.

Dr. Thorpe and his colleague, Zhou Yang, Ph.D., proposed an evidence-based weight loss program for individuals aged 60-64 who are not yet eligible for Medicare but who are overweight (BMI higher than 24) or obese and at risk for diabetes, cardiovascular disease, or both (Health Affairs 2011 [doi:10.1377/hlthaff.2010.0944]).

Specifically, they suggested expanding an existing community-based weight loss program developed by the CDC, the YMCA of the USA, and UnitedHealth Group, in which trained lifestyle coaches help overweight individuals select healthier foods and increase physical activity. The program is provided by 50 YMCAs and is available at more than 116 sites in 24 states. Studies of this and similar programs show that participants aged 60 years and older lose weight and reduce their risk of developing diabetes by up to 71%.

For the current study, the investigators used 2009 census data to estimate net savings to Medicare over a 10-year period over the lifetime of a single cohort of eligible individuals. Their findings were based on the assumption of participation rates of 70% and 55% of eligible individuals using two enrollment scenarios.

The first scenario would limit enrollment to individuals ages 60-64 who have prediabetes and whose BMI is higher than 24. The cost to enroll 70% of that target group would be about $590 million ($240 per person for 2.6 million participants) but would result in a net savings of $2.3 billion over 10 years and $9.3 billion in net lifetime savings. If 55% of those eligible participated, estimated savings would exceed $1.8 billion over 10 years and $7.3 billion in net lifetime savings.

The second scenario would broaden eligibility to individuals with the same BMI who were at risk for cardiovascular complications (high blood pressure or elevated cholesterol) regardless of whether they had prediabetes. If 70% of eligible patients participate, Medicare would achieve an estimated net savings of $1.4 billion over 10 years and $5.8 billion in net lifetime savings. If 55% of eligible patients participate, the estimated additional net savings to Medicare would be $1.2 billion over 10 years and $4.6 billion over participants' lifetimes.

By extending eligibility to both at-risk groups, the authors estimate that Medicare would save $3 billion to $3.7 billion over the next 10 years and $11.9 to $15.1 billion over participants' lifetimes, depending on the participation rate.

“Our results show the potential savings to Medicare if a proven community-based approach to reducing obesity and related chronic disease were to be made available, nationwide, to high-risk individuals soon to become Medicare beneficiaries,” the researchers said. “In doing so, they also present a potential business case for the federal government to partner with the private sector in order to encourage broad enrollment in effective weight loss programs.”Estimated lifetime savings of $7 billion to $15 billion depend on several factors, such eligibility and participation, they said.