Mary Ann Moon

Adjuvant corticosteroid therapy did not improve survival or shorten hospitalization in the largest observational study of its kind ever conducted in children, researchers reported.

These findings held true across all pediatric age groups and regardless of whether the infecting organism was pneumococcal or meningococcal, according to Jillian Mongelluzzo of the division of infectious diseases, Children's Hospital of Philadelphia, and her associates.

Adjuvant corticosteroid therapy does reduce hearing loss in children with meningitis caused by Haemophilus influenzae type b (Hib), but since the widespread use of vaccines against Hib in 1985 and Streptococcus pneumoniae in 2000, the epidemiology of bacterial meningitis has changed dramatically, they said.

Nonetheless, the use of adjuvant corticosteroid therapy appears to be increasing, so “a randomized trial is warranted to explore the possible benefit … before such corticosteroid use becomes routine,” the investigators noted (JAMA 2008;299:2048–55).

In this retrospective cohort study, the investigators used data from the Pediatric Health Information System, a database that covers 27 tertiary care children's hospitals across the country, to track meningitis trends from 2001 through 2006 in areas where Hib meningitis is no longer prevalent.

In all, 2,780 cases of bacterial meningitis in children younger than 18 years were assessed.

Adjuvant corticosteroids, most often dexamethasone, were given to 248 children (9%). The use of these agents increased steadily over time, from 5.8% of patients in 2001 to 12.2% in 2006.

Use varied greatly by hospital, with some centers never giving adjuvant corticosteroids and one giving them in 37% of cases, Ms. Mongelluzzo and her associates said.

There were 15 deaths among children who received corticosteroids (6% mortality) and 102 among the 2,532 children who did not (4% mortality), a difference that was not statistically significant.

The treatment did not improve survival when the data were analyzed by age group, nor did it affect the length of the interval between admission and death, Dr. Mongelluzzo and her associates said.

The median length of stay for children who received corticosteroids was 12 days (range 7–21 days), while the median for children who did not receive corticosteroids was 10 days (range 6–20 days)—a difference that also was not statistically significant.

Length of stay is important to consider because “longer hospitalizations increase the risk of hospital-acquired complications,” the investigators said.

These results did not change when the data were analyzed by type of infecting organism, including Hib, S. pneumoniae, and Neisseria meningitidis, and others.

It is not yet clear why corticosteroids do not improve survival in children as they do in adults.

Adults may have different predisposing factors for meningitis or a different inflammatory response, which could change their course of disease in comparison with children, Ms. Mongelluzzo and her associates noted.

They added that this study did not address the possible benefits of adjuvant corticosteroid therapy on hearing loss or neurologic morbidity in children.

Adjuvant corticosteroid therapy did not improve survival or shorten hospitalization in the largest observational study of its kind ever conducted in children, researchers reported.

These findings held true across all pediatric age groups and regardless of whether the infecting organism was pneumococcal or meningococcal, according to Jillian Mongelluzzo of the division of infectious diseases, Children's Hospital of Philadelphia, and her associates.

Adjuvant corticosteroid therapy does reduce hearing loss in children with meningitis caused by Haemophilus influenzae type b (Hib), but since the widespread use of vaccines against Hib in 1985 and Streptococcus pneumoniae in 2000, the epidemiology of bacterial meningitis has changed dramatically, they said.

Nonetheless, the use of adjuvant corticosteroid therapy appears to be increasing, so “a randomized trial is warranted to explore the possible benefit … before such corticosteroid use becomes routine,” the investigators noted (JAMA 2008;299:2048–55).

In this retrospective cohort study, the investigators used data from the Pediatric Health Information System, a database that covers 27 tertiary care children's hospitals across the country, to track meningitis trends from 2001 through 2006 in areas where Hib meningitis is no longer prevalent.

In all, 2,780 cases of bacterial meningitis in children younger than 18 years were assessed.

Adjuvant corticosteroids, most often dexamethasone, were given to 248 children (9%). The use of these agents increased steadily over time, from 5.8% of patients in 2001 to 12.2% in 2006.

Use varied greatly by hospital, with some centers never giving adjuvant corticosteroids and one giving them in 37% of cases, Ms. Mongelluzzo and her associates said.

There were 15 deaths among children who received corticosteroids (6% mortality) and 102 among the 2,532 children who did not (4% mortality), a difference that was not statistically significant.

The treatment did not improve survival when the data were analyzed by age group, nor did it affect the length of the interval between admission and death, Dr. Mongelluzzo and her associates said.

The median length of stay for children who received corticosteroids was 12 days (range 7–21 days), while the median for children who did not receive corticosteroids was 10 days (range 6–20 days)—a difference that also was not statistically significant.

Length of stay is important to consider because “longer hospitalizations increase the risk of hospital-acquired complications,” the investigators said.

These results did not change when the data were analyzed by type of infecting organism, including Hib, S. pneumoniae, and Neisseria meningitidis, and others.

It is not yet clear why corticosteroids do not improve survival in children as they do in adults.

Adults may have different predisposing factors for meningitis or a different inflammatory response, which could change their course of disease in comparison with children, Ms. Mongelluzzo and her associates noted.

They added that this study did not address the possible benefits of adjuvant corticosteroid therapy on hearing loss or neurologic morbidity in children.

Adjuvant corticosteroid therapy did not improve survival or shorten hospitalization in the largest observational study of its kind ever conducted in children, researchers reported.

These findings held true across all pediatric age groups and regardless of whether the infecting organism was pneumococcal or meningococcal, according to Jillian Mongelluzzo of the division of infectious diseases, Children's Hospital of Philadelphia, and her associates.

Adjuvant corticosteroid therapy does reduce hearing loss in children with meningitis caused by Haemophilus influenzae type b (Hib), but since the widespread use of vaccines against Hib in 1985 and Streptococcus pneumoniae in 2000, the epidemiology of bacterial meningitis has changed dramatically, they said.

Nonetheless, the use of adjuvant corticosteroid therapy appears to be increasing, so “a randomized trial is warranted to explore the possible benefit … before such corticosteroid use becomes routine,” the investigators noted (JAMA 2008;299:2048–55).

In this retrospective cohort study, the investigators used data from the Pediatric Health Information System, a database that covers 27 tertiary care children's hospitals across the country, to track meningitis trends from 2001 through 2006 in areas where Hib meningitis is no longer prevalent.

In all, 2,780 cases of bacterial meningitis in children younger than 18 years were assessed.

Adjuvant corticosteroids, most often dexamethasone, were given to 248 children (9%). The use of these agents increased steadily over time, from 5.8% of patients in 2001 to 12.2% in 2006.

Use varied greatly by hospital, with some centers never giving adjuvant corticosteroids and one giving them in 37% of cases, Ms. Mongelluzzo and her associates said.

There were 15 deaths among children who received corticosteroids (6% mortality) and 102 among the 2,532 children who did not (4% mortality), a difference that was not statistically significant.

The treatment did not improve survival when the data were analyzed by age group, nor did it affect the length of the interval between admission and death, Dr. Mongelluzzo and her associates said.

The median length of stay for children who received corticosteroids was 12 days (range 7–21 days), while the median for children who did not receive corticosteroids was 10 days (range 6–20 days)—a difference that also was not statistically significant.

Length of stay is important to consider because “longer hospitalizations increase the risk of hospital-acquired complications,” the investigators said.

These results did not change when the data were analyzed by type of infecting organism, including Hib, S. pneumoniae, and Neisseria meningitidis, and others.

It is not yet clear why corticosteroids do not improve survival in children as they do in adults.

Adults may have different predisposing factors for meningitis or a different inflammatory response, which could change their course of disease in comparison with children, Ms. Mongelluzzo and her associates noted.

They added that this study did not address the possible benefits of adjuvant corticosteroid therapy on hearing loss or neurologic morbidity in children.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in a large international study.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes, as well as a host of neonatal problems that included hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” said Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study.

The investigators assessed 23,316 pregnant women in an effort “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.”

The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems were found to increase as the plasma glucose levels increased, the investigators reported (N. Engl. J. Med. 2008;358:1991–2002).

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (the need for cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes.

A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in a large international study.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes, as well as a host of neonatal problems that included hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” said Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study.

The investigators assessed 23,316 pregnant women in an effort “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.”

The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems were found to increase as the plasma glucose levels increased, the investigators reported (N. Engl. J. Med. 2008;358:1991–2002).

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (the need for cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes.

A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in a large international study.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes, as well as a host of neonatal problems that included hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” said Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study.

The investigators assessed 23,316 pregnant women in an effort “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.”

The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems were found to increase as the plasma glucose levels increased, the investigators reported (N. Engl. J. Med. 2008;358:1991–2002).

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (the need for cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes.

A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

Naproxen and celecoxib failed to prevent Alzheimer's disease in the first clinical trial to test the agents as preventives in older subjects who had no cognitive impairment, wrote Barbara K. Martin, Ph.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Epidemiologic data suggest that prolonged NSAID use might protect against age-related cognitive decline, a possible forerunner of Alzheimer's disease, but small observational studies have yielded conflicting results.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), sponsored by the National Institute on Aging, was a placebo-controlled clinical trial designed to assess naproxen and celecoxib in 2,528 cognitively normal men and women aged 70 or older. A total of 726 were allocated to celecoxib, 719 to naproxen, and 1,083 to placebo. The study was halted early “after increased cardiovascular risk was observed with celecoxib in another prevention trial,” the investigators said (Arch. Neurol. 2008 May 12 [doi:10.1001/archneur.2008.65.7.nct70006]).

A total of 2,117 subjects contributed follow-up cognitive measures for at least 6 months after discontinuing the study medications.

Subjects' scores on the Modified Mini-Mental State Examination, a measure of global cognitive function, were significantly lower for both treatment groups than for the placebo group (−0.32 points for celecoxib and −0.36 points for naproxen), Dr. Martin and her associates said.

To put their findings in a clinical context, the researchers noted that the differences in cognitive scores between the treatment groups and the placebo group are equivalent to the average yearly decline among normal elderly subjects.

Naproxen and celecoxib failed to prevent Alzheimer's disease in the first clinical trial to test the agents as preventives in older subjects who had no cognitive impairment, wrote Barbara K. Martin, Ph.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Epidemiologic data suggest that prolonged NSAID use might protect against age-related cognitive decline, a possible forerunner of Alzheimer's disease, but small observational studies have yielded conflicting results.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), sponsored by the National Institute on Aging, was a placebo-controlled clinical trial designed to assess naproxen and celecoxib in 2,528 cognitively normal men and women aged 70 or older. A total of 726 were allocated to celecoxib, 719 to naproxen, and 1,083 to placebo. The study was halted early “after increased cardiovascular risk was observed with celecoxib in another prevention trial,” the investigators said (Arch. Neurol. 2008 May 12 [doi:10.1001/archneur.2008.65.7.nct70006]).

A total of 2,117 subjects contributed follow-up cognitive measures for at least 6 months after discontinuing the study medications.

Subjects' scores on the Modified Mini-Mental State Examination, a measure of global cognitive function, were significantly lower for both treatment groups than for the placebo group (−0.32 points for celecoxib and −0.36 points for naproxen), Dr. Martin and her associates said.

To put their findings in a clinical context, the researchers noted that the differences in cognitive scores between the treatment groups and the placebo group are equivalent to the average yearly decline among normal elderly subjects.

Naproxen and celecoxib failed to prevent Alzheimer's disease in the first clinical trial to test the agents as preventives in older subjects who had no cognitive impairment, wrote Barbara K. Martin, Ph.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Epidemiologic data suggest that prolonged NSAID use might protect against age-related cognitive decline, a possible forerunner of Alzheimer's disease, but small observational studies have yielded conflicting results.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), sponsored by the National Institute on Aging, was a placebo-controlled clinical trial designed to assess naproxen and celecoxib in 2,528 cognitively normal men and women aged 70 or older. A total of 726 were allocated to celecoxib, 719 to naproxen, and 1,083 to placebo. The study was halted early “after increased cardiovascular risk was observed with celecoxib in another prevention trial,” the investigators said (Arch. Neurol. 2008 May 12 [doi:10.1001/archneur.2008.65.7.nct70006]).

A total of 2,117 subjects contributed follow-up cognitive measures for at least 6 months after discontinuing the study medications.

Subjects' scores on the Modified Mini-Mental State Examination, a measure of global cognitive function, were significantly lower for both treatment groups than for the placebo group (−0.32 points for celecoxib and −0.36 points for naproxen), Dr. Martin and her associates said.

To put their findings in a clinical context, the researchers noted that the differences in cognitive scores between the treatment groups and the placebo group are equivalent to the average yearly decline among normal elderly subjects.

Both the presence and severity of depression are associated with decreased serum levels of 25-hydroxyvitamin D and increased levels of parathyroid hormone in older patients, researchers reported.

It is not yet known whether abnormal levels of 25(OH)D and PTH precede depression or are a consequence of it, they noted.

“Our findings may be of clinical relevance because the prevalence of minor depression in older persons is high (13%), and both decreased serum 25(OH)D levels and increased serum PTH levels can, in theory, be treated with higher dietary intake of vitamin D or calcium and increased exposure to daylight,” said Dr. Witte J.G. Hoogendijk and his associates at the Free University Medical Center, Amsterdam.

The investigators examined the relationship between depression and these serum markers using data from the Longitudinal Aging Study Amsterdam, an ongoing population-based study of changes in mood, autonomy, and well-being among older Dutch men and women.

In a subset of 1,282 of these subjects who were aged 65–95 years, 26 were found to have major depressive disorder and 169 were found to have minor depression.

Levels of 25(OH)D were 14% lower in people with minor depression and in people with major depression than in nondepressed people. PTH levels were 5% higher in people with minor depression and 33% higher in people with major depression than in nondepressed people, Dr. Hoogendijk and associates said (Arch. Gen. Psychiatry 2008;65:508-12).

These associations remained robust after the data were adjusted to account for several potential confounders such as gender, body mass index, smoking status, and coexisting chronic conditions. They also were not attributable to seasonal differences regarding when the assessments were done (and thus the amount of sunlight to which subjects had been recently exposed), to levels of physical activity, or to the use of antidepressants.

The importance of these results is underscored by the finding that 39% of men and 57% of women in this community-based cohort were obtaining insufficient vitamin D from their diets, including 5% of men and 7% of women who were frankly deficient in vitamin D. Only 1% of subjects were taking vitamin D or calcium supplements.

The study was supported by the Netherlands Organisation for Scientific Research.

Both the presence and severity of depression are associated with decreased serum levels of 25-hydroxyvitamin D and increased levels of parathyroid hormone in older patients, researchers reported.

It is not yet known whether abnormal levels of 25(OH)D and PTH precede depression or are a consequence of it, they noted.

“Our findings may be of clinical relevance because the prevalence of minor depression in older persons is high (13%), and both decreased serum 25(OH)D levels and increased serum PTH levels can, in theory, be treated with higher dietary intake of vitamin D or calcium and increased exposure to daylight,” said Dr. Witte J.G. Hoogendijk and his associates at the Free University Medical Center, Amsterdam.

The investigators examined the relationship between depression and these serum markers using data from the Longitudinal Aging Study Amsterdam, an ongoing population-based study of changes in mood, autonomy, and well-being among older Dutch men and women.

In a subset of 1,282 of these subjects who were aged 65–95 years, 26 were found to have major depressive disorder and 169 were found to have minor depression.

Levels of 25(OH)D were 14% lower in people with minor depression and in people with major depression than in nondepressed people. PTH levels were 5% higher in people with minor depression and 33% higher in people with major depression than in nondepressed people, Dr. Hoogendijk and associates said (Arch. Gen. Psychiatry 2008;65:508-12).

These associations remained robust after the data were adjusted to account for several potential confounders such as gender, body mass index, smoking status, and coexisting chronic conditions. They also were not attributable to seasonal differences regarding when the assessments were done (and thus the amount of sunlight to which subjects had been recently exposed), to levels of physical activity, or to the use of antidepressants.

The importance of these results is underscored by the finding that 39% of men and 57% of women in this community-based cohort were obtaining insufficient vitamin D from their diets, including 5% of men and 7% of women who were frankly deficient in vitamin D. Only 1% of subjects were taking vitamin D or calcium supplements.

The study was supported by the Netherlands Organisation for Scientific Research.

Both the presence and severity of depression are associated with decreased serum levels of 25-hydroxyvitamin D and increased levels of parathyroid hormone in older patients, researchers reported.

It is not yet known whether abnormal levels of 25(OH)D and PTH precede depression or are a consequence of it, they noted.

“Our findings may be of clinical relevance because the prevalence of minor depression in older persons is high (13%), and both decreased serum 25(OH)D levels and increased serum PTH levels can, in theory, be treated with higher dietary intake of vitamin D or calcium and increased exposure to daylight,” said Dr. Witte J.G. Hoogendijk and his associates at the Free University Medical Center, Amsterdam.

The investigators examined the relationship between depression and these serum markers using data from the Longitudinal Aging Study Amsterdam, an ongoing population-based study of changes in mood, autonomy, and well-being among older Dutch men and women.

In a subset of 1,282 of these subjects who were aged 65–95 years, 26 were found to have major depressive disorder and 169 were found to have minor depression.

Levels of 25(OH)D were 14% lower in people with minor depression and in people with major depression than in nondepressed people. PTH levels were 5% higher in people with minor depression and 33% higher in people with major depression than in nondepressed people, Dr. Hoogendijk and associates said (Arch. Gen. Psychiatry 2008;65:508-12).

These associations remained robust after the data were adjusted to account for several potential confounders such as gender, body mass index, smoking status, and coexisting chronic conditions. They also were not attributable to seasonal differences regarding when the assessments were done (and thus the amount of sunlight to which subjects had been recently exposed), to levels of physical activity, or to the use of antidepressants.

The importance of these results is underscored by the finding that 39% of men and 57% of women in this community-based cohort were obtaining insufficient vitamin D from their diets, including 5% of men and 7% of women who were frankly deficient in vitamin D. Only 1% of subjects were taking vitamin D or calcium supplements.

The study was supported by the Netherlands Organisation for Scientific Research.

Endotracheal tubes coated with silver, which has shown potent broad-spectrum antimicrobial activity in vitro, reduced the incidence of ventilator-associated pneumonia by 35% in a multicenter study, researchers reported.

“This is the first intervention demonstrated to reduce ventilator-associated pneumonia [VAP] incidence that does not require more effort or supervision from clinicians providing bedside care,” said Dr. Marin H. Kollef of Washington University, St. Louis, and associates.

However, the reduced rate of pneumonia did not translate into decreased mortality, duration of intubation, duration of ICU stay, duration of hospitalization, or frequency or severity of the adverse effects of intubation.

In an editorial comment, Dr. Jean Chastre said that physicians should “probably” consider using silver-coated endotracheal tubes for “the subset of patients at very high risk of developing early-onset VAP, such as neurologically impaired patients or trauma patients.” But the value of the device for other patients, particularly those who might need prolonged ventilation, has not yet been shown.

Dr. Kollef and associates compared the silver-coated endotracheal tube with standard tubes in a prospective trial sponsored by the device manufacturer, C.R. Bard Inc. A total of 1,509 patients requiring mechanical ventilation for 24 hours or longer were treated at 54 medical centers.

Microbiologically confirmed VAP developed in 4.8% of patients using the silver-coated tube, compared with 7.5% of those using the standard tube—a relative risk reduction of 35.9% and an absolute risk reduction of 2.7%.

The number of patients needed to be treated with the silver-coated tube to prevent one case of VAP was 37, the investigators said (JAMA 2008;300:805–13).

The device appeared to be most effective in preventing VAP during the first 10 days of intubation, “which is clinically relevant because the median duration of intubation is less than 10 days, and more than 75% of patients are extubated before 10 days,” Dr. Kollef and colleagues said.

Mortality was not significantly different between patients who used the silver-coated tube (30%) and those who used standard tubes (27%). There also were no significant differences between the two groups in duration of intubation, ICU stay, or hospital stay, or in the frequency and severity of adverse events related to endotracheal intubation.

This lack of between-group differences might have been related to the unusually low rate of VAP in the control group, which was approximately half of the expected rate of 15%, the investigators noted.

In his editorial comment, Dr. Chastre of the University of Pierre and Marie Curie, Paris, noted that more than 7,000 potential subjects were screened but not enrolled in the trial because they were unable to provide informed consent within the time frame necessary for emergency intubation or were unlikely to require intubation for 24 hours or longer. This threatens both the external validity of the trial and its clinical relevance, he said.

Moreover, the number of cases of VAP was so low that the addition of only three cases among patients using the silver-coated tube “would have sufficed to render the trial statistically inconclusive,” Dr. Chastre wrote (JAMA 2008;300:842–4).

In addition, there was a statistically significant imbalance in the proportion of patients who had preexisting chronic obstructive pulmonary disease between the two groups, which favored the group using the silver-coated tube. And the number of cases of late-onset VAP—pneumonia developing after 7 days of mechanical ventilation—was so small that it limited the study's ability to show efficacy with prolonged intubation.

“Consequently, silver-coated tubes should not be viewed as the definitive answer for VAP prevention, and, until additional data confirm the clinical effectiveness and cost benefit of these devices, their use should be restricted to high-risk patients” in ICUs with low background infection rates, Dr. Chastre noted.

All the authors of this study received grant support from Bard, and Dr. Kollef and Dr. Chastre have received fees from other companies.

Endotracheal tubes coated with silver, which has shown potent broad-spectrum antimicrobial activity in vitro, reduced the incidence of ventilator-associated pneumonia by 35% in a multicenter study, researchers reported.

“This is the first intervention demonstrated to reduce ventilator-associated pneumonia [VAP] incidence that does not require more effort or supervision from clinicians providing bedside care,” said Dr. Marin H. Kollef of Washington University, St. Louis, and associates.

However, the reduced rate of pneumonia did not translate into decreased mortality, duration of intubation, duration of ICU stay, duration of hospitalization, or frequency or severity of the adverse effects of intubation.

In an editorial comment, Dr. Jean Chastre said that physicians should “probably” consider using silver-coated endotracheal tubes for “the subset of patients at very high risk of developing early-onset VAP, such as neurologically impaired patients or trauma patients.” But the value of the device for other patients, particularly those who might need prolonged ventilation, has not yet been shown.

Dr. Kollef and associates compared the silver-coated endotracheal tube with standard tubes in a prospective trial sponsored by the device manufacturer, C.R. Bard Inc. A total of 1,509 patients requiring mechanical ventilation for 24 hours or longer were treated at 54 medical centers.

Microbiologically confirmed VAP developed in 4.8% of patients using the silver-coated tube, compared with 7.5% of those using the standard tube—a relative risk reduction of 35.9% and an absolute risk reduction of 2.7%.

The number of patients needed to be treated with the silver-coated tube to prevent one case of VAP was 37, the investigators said (JAMA 2008;300:805–13).

The device appeared to be most effective in preventing VAP during the first 10 days of intubation, “which is clinically relevant because the median duration of intubation is less than 10 days, and more than 75% of patients are extubated before 10 days,” Dr. Kollef and colleagues said.

Mortality was not significantly different between patients who used the silver-coated tube (30%) and those who used standard tubes (27%). There also were no significant differences between the two groups in duration of intubation, ICU stay, or hospital stay, or in the frequency and severity of adverse events related to endotracheal intubation.

This lack of between-group differences might have been related to the unusually low rate of VAP in the control group, which was approximately half of the expected rate of 15%, the investigators noted.

In his editorial comment, Dr. Chastre of the University of Pierre and Marie Curie, Paris, noted that more than 7,000 potential subjects were screened but not enrolled in the trial because they were unable to provide informed consent within the time frame necessary for emergency intubation or were unlikely to require intubation for 24 hours or longer. This threatens both the external validity of the trial and its clinical relevance, he said.

Moreover, the number of cases of VAP was so low that the addition of only three cases among patients using the silver-coated tube “would have sufficed to render the trial statistically inconclusive,” Dr. Chastre wrote (JAMA 2008;300:842–4).

In addition, there was a statistically significant imbalance in the proportion of patients who had preexisting chronic obstructive pulmonary disease between the two groups, which favored the group using the silver-coated tube. And the number of cases of late-onset VAP—pneumonia developing after 7 days of mechanical ventilation—was so small that it limited the study's ability to show efficacy with prolonged intubation.

“Consequently, silver-coated tubes should not be viewed as the definitive answer for VAP prevention, and, until additional data confirm the clinical effectiveness and cost benefit of these devices, their use should be restricted to high-risk patients” in ICUs with low background infection rates, Dr. Chastre noted.

All the authors of this study received grant support from Bard, and Dr. Kollef and Dr. Chastre have received fees from other companies.

Endotracheal tubes coated with silver, which has shown potent broad-spectrum antimicrobial activity in vitro, reduced the incidence of ventilator-associated pneumonia by 35% in a multicenter study, researchers reported.

“This is the first intervention demonstrated to reduce ventilator-associated pneumonia [VAP] incidence that does not require more effort or supervision from clinicians providing bedside care,” said Dr. Marin H. Kollef of Washington University, St. Louis, and associates.

However, the reduced rate of pneumonia did not translate into decreased mortality, duration of intubation, duration of ICU stay, duration of hospitalization, or frequency or severity of the adverse effects of intubation.

In an editorial comment, Dr. Jean Chastre said that physicians should “probably” consider using silver-coated endotracheal tubes for “the subset of patients at very high risk of developing early-onset VAP, such as neurologically impaired patients or trauma patients.” But the value of the device for other patients, particularly those who might need prolonged ventilation, has not yet been shown.

Dr. Kollef and associates compared the silver-coated endotracheal tube with standard tubes in a prospective trial sponsored by the device manufacturer, C.R. Bard Inc. A total of 1,509 patients requiring mechanical ventilation for 24 hours or longer were treated at 54 medical centers.

Microbiologically confirmed VAP developed in 4.8% of patients using the silver-coated tube, compared with 7.5% of those using the standard tube—a relative risk reduction of 35.9% and an absolute risk reduction of 2.7%.

The number of patients needed to be treated with the silver-coated tube to prevent one case of VAP was 37, the investigators said (JAMA 2008;300:805–13).

The device appeared to be most effective in preventing VAP during the first 10 days of intubation, “which is clinically relevant because the median duration of intubation is less than 10 days, and more than 75% of patients are extubated before 10 days,” Dr. Kollef and colleagues said.

Mortality was not significantly different between patients who used the silver-coated tube (30%) and those who used standard tubes (27%). There also were no significant differences between the two groups in duration of intubation, ICU stay, or hospital stay, or in the frequency and severity of adverse events related to endotracheal intubation.

This lack of between-group differences might have been related to the unusually low rate of VAP in the control group, which was approximately half of the expected rate of 15%, the investigators noted.

In his editorial comment, Dr. Chastre of the University of Pierre and Marie Curie, Paris, noted that more than 7,000 potential subjects were screened but not enrolled in the trial because they were unable to provide informed consent within the time frame necessary for emergency intubation or were unlikely to require intubation for 24 hours or longer. This threatens both the external validity of the trial and its clinical relevance, he said.

Moreover, the number of cases of VAP was so low that the addition of only three cases among patients using the silver-coated tube “would have sufficed to render the trial statistically inconclusive,” Dr. Chastre wrote (JAMA 2008;300:842–4).

In addition, there was a statistically significant imbalance in the proportion of patients who had preexisting chronic obstructive pulmonary disease between the two groups, which favored the group using the silver-coated tube. And the number of cases of late-onset VAP—pneumonia developing after 7 days of mechanical ventilation—was so small that it limited the study's ability to show efficacy with prolonged intubation.

“Consequently, silver-coated tubes should not be viewed as the definitive answer for VAP prevention, and, until additional data confirm the clinical effectiveness and cost benefit of these devices, their use should be restricted to high-risk patients” in ICUs with low background infection rates, Dr. Chastre noted.

All the authors of this study received grant support from Bard, and Dr. Kollef and Dr. Chastre have received fees from other companies.

Positive immunostaining with monoclonal antibody D2–40, together with younger patient age and lesion ulceration, might identify which melanoma patients are likely to have nodal metastasis and should undergo sentinel node biopsy, according to Dr. Firouzeh Niakosari of Sunnybrook Health Sciences Centre, Toronto, and associates.

"The recently developed monoclonal antibody [Mab] D2–40 reacts with endothelial cells of lymphatics but not with endothelial cells of blood vessels in normal tissues," the investigators wrote (Arch. Dermatol. 2008;144:462–7).

Mab D2–40 immunostaining more readily identifies lymphatic invasion in primary melanomas than does conventional staining with hematoxylin-eosin. Dr. Niakosari and associates assessed the technique's predictive value using blocks of primary tumor taken from 96 patients who were treated in 1998–2004 and had no clinical evidence of metastasis.

On biopsy, sentinel lymph nodes had been found to be positive in 23 of the cases.

Mab D2–40 immunostaining was positive for invasion of the lymphatic vessels within the tumor samples in 32 of the 96 cases (33%). The result was correct in ruling out lymphatic invasion in 56 (77%) of the cases that proved to have no invasion on sentinel node biopsy, and it was correct in identifying lymphatic invasion in 15 (65%) of the cases that did have lymphatic invasion on sentinel node biopsy.

On its own, then, the technique had a negative predictive value of 88% and a positive predictive value of 47%, the investigators found.

Mab D2–40 immunostaining was even more predictive when the results were combined with two clinical factors: younger patient age and the presence of ulceration in the lesion. "The probability of sentinel lymph node positivity was 13% when lymphatic invasion identified by immunostaining with Mab D2–40 was negative, no ulceration was present, and the patient was 50 years or older," they noted.

In cases in which the immunostaining indicated that there was lymphatic invasion, ulceration was present, and the patient was younger than 50 years, the probability of sentinel lymph node positivity increased to 61%, Dr. Niakosari and associates reported.

Lymphatic invasion on Mab D2–40 immunostaining correlated with deeper Clark Level of Invasion and increased Breslow tumor thickness, "indicating that lymphatic invasion occurs more frequently in later stages of melanoma," they wrote.

Positive immunostaining with monoclonal antibody D2–40, together with younger patient age and lesion ulceration, might identify which melanoma patients are likely to have nodal metastasis and should undergo sentinel node biopsy, according to Dr. Firouzeh Niakosari of Sunnybrook Health Sciences Centre, Toronto, and associates.

"The recently developed monoclonal antibody [Mab] D2–40 reacts with endothelial cells of lymphatics but not with endothelial cells of blood vessels in normal tissues," the investigators wrote (Arch. Dermatol. 2008;144:462–7).

Mab D2–40 immunostaining more readily identifies lymphatic invasion in primary melanomas than does conventional staining with hematoxylin-eosin. Dr. Niakosari and associates assessed the technique's predictive value using blocks of primary tumor taken from 96 patients who were treated in 1998–2004 and had no clinical evidence of metastasis.

On biopsy, sentinel lymph nodes had been found to be positive in 23 of the cases.

Mab D2–40 immunostaining was positive for invasion of the lymphatic vessels within the tumor samples in 32 of the 96 cases (33%). The result was correct in ruling out lymphatic invasion in 56 (77%) of the cases that proved to have no invasion on sentinel node biopsy, and it was correct in identifying lymphatic invasion in 15 (65%) of the cases that did have lymphatic invasion on sentinel node biopsy.

On its own, then, the technique had a negative predictive value of 88% and a positive predictive value of 47%, the investigators found.

Mab D2–40 immunostaining was even more predictive when the results were combined with two clinical factors: younger patient age and the presence of ulceration in the lesion. "The probability of sentinel lymph node positivity was 13% when lymphatic invasion identified by immunostaining with Mab D2–40 was negative, no ulceration was present, and the patient was 50 years or older," they noted.

In cases in which the immunostaining indicated that there was lymphatic invasion, ulceration was present, and the patient was younger than 50 years, the probability of sentinel lymph node positivity increased to 61%, Dr. Niakosari and associates reported.

Lymphatic invasion on Mab D2–40 immunostaining correlated with deeper Clark Level of Invasion and increased Breslow tumor thickness, "indicating that lymphatic invasion occurs more frequently in later stages of melanoma," they wrote.

Positive immunostaining with monoclonal antibody D2–40, together with younger patient age and lesion ulceration, might identify which melanoma patients are likely to have nodal metastasis and should undergo sentinel node biopsy, according to Dr. Firouzeh Niakosari of Sunnybrook Health Sciences Centre, Toronto, and associates.

"The recently developed monoclonal antibody [Mab] D2–40 reacts with endothelial cells of lymphatics but not with endothelial cells of blood vessels in normal tissues," the investigators wrote (Arch. Dermatol. 2008;144:462–7).

Mab D2–40 immunostaining more readily identifies lymphatic invasion in primary melanomas than does conventional staining with hematoxylin-eosin. Dr. Niakosari and associates assessed the technique's predictive value using blocks of primary tumor taken from 96 patients who were treated in 1998–2004 and had no clinical evidence of metastasis.

On biopsy, sentinel lymph nodes had been found to be positive in 23 of the cases.

Mab D2–40 immunostaining was positive for invasion of the lymphatic vessels within the tumor samples in 32 of the 96 cases (33%). The result was correct in ruling out lymphatic invasion in 56 (77%) of the cases that proved to have no invasion on sentinel node biopsy, and it was correct in identifying lymphatic invasion in 15 (65%) of the cases that did have lymphatic invasion on sentinel node biopsy.

On its own, then, the technique had a negative predictive value of 88% and a positive predictive value of 47%, the investigators found.

Mab D2–40 immunostaining was even more predictive when the results were combined with two clinical factors: younger patient age and the presence of ulceration in the lesion. "The probability of sentinel lymph node positivity was 13% when lymphatic invasion identified by immunostaining with Mab D2–40 was negative, no ulceration was present, and the patient was 50 years or older," they noted.

In cases in which the immunostaining indicated that there was lymphatic invasion, ulceration was present, and the patient was younger than 50 years, the probability of sentinel lymph node positivity increased to 61%, Dr. Niakosari and associates reported.

Lymphatic invasion on Mab D2–40 immunostaining correlated with deeper Clark Level of Invasion and increased Breslow tumor thickness, "indicating that lymphatic invasion occurs more frequently in later stages of melanoma," they wrote.

The rates at which oral antibiotics were prescribed to children under age 5 years were directly related to the rates of resistant Streptococcus pneumoniae cultured from acute otitis media cases in a study reviewing more than 200,000 prescriptions.

In two distinct populations in southern Israel that were followed for 5 successive years, a “remarkable” seasonal reduction in antibiotic prescriptions during the warm months was significantly associated with a marked reduction in antibiotic resistance rates in pneumococcal isolates, said Dr. Ron Dagan of Soroka University Medical Center, Beer-Sheva, Israel, and his associates (J. Infect. Dis. 2008;197:1094-102).

“In Jewish children, each monthly increase in 10 prescriptions per 1,000 children was associated with a 1.05-fold increase in the odds of penicillin resistance during that month. The corresponding odds ratio for erythromycin resistance was 1.04, and for multidrug resistance it was 1.04,” they wrote.

In an accompanying editorial, Dr. Cindy R. Friedman and Dr. Cynthia G. Whitney of the Centers for Disease Control and Prevention, Atlanta, wrote that these findings provide solid evidence that reducing antibiotic use can lead to a decrease in resistant pneumococcal infections. “The challenge now is for clinicians to reduce unnecessary use” of antibiotics, they wrote (J. Infect. Dis. 2008;197:1082-3).

The researchers reviewed all 236,466 prescriptions for oral antibiotics written during 1999-2003 for children aged younger than 5 years in seven large pediatric primary care clinics. Five of these were in urban Jewish centers and two in Bedouin townships. There was a 24% drop in the prescription rate during the warm months, compared with the cold months. The mean monthly antibiotic prescription rate was 291 per 1,000 children in the winter and 222 per 1,000 in the summer. Rates of antibiotic resistance showed a corresponding seasonal variation.

Although this pattern was seen in both populations, the urban Jewish population showed a much more pronounced—and statistically significant—seasonal variation in both prescribing rates and resistance rates than did the rural Bedouin population.

In the Jewish population, the rate of penicillin resistance was 43% in the cold months, compared with 29% in the warm months. The rate of erythromycin resistance was 29% in the cold months, compared with 20% in the warm months. And the rate of multidrug resistance was 25% in the cold months, compared with 15%. The differences were smaller and not statistically significant in Bedouin children.

These findings suggest that interventions to reduce antibiotic overuse “may reduce resistance in the community faster than previously thought,” they added.

The rates at which oral antibiotics were prescribed to children under age 5 years were directly related to the rates of resistant Streptococcus pneumoniae cultured from acute otitis media cases in a study reviewing more than 200,000 prescriptions.

In two distinct populations in southern Israel that were followed for 5 successive years, a “remarkable” seasonal reduction in antibiotic prescriptions during the warm months was significantly associated with a marked reduction in antibiotic resistance rates in pneumococcal isolates, said Dr. Ron Dagan of Soroka University Medical Center, Beer-Sheva, Israel, and his associates (J. Infect. Dis. 2008;197:1094-102).

“In Jewish children, each monthly increase in 10 prescriptions per 1,000 children was associated with a 1.05-fold increase in the odds of penicillin resistance during that month. The corresponding odds ratio for erythromycin resistance was 1.04, and for multidrug resistance it was 1.04,” they wrote.

In an accompanying editorial, Dr. Cindy R. Friedman and Dr. Cynthia G. Whitney of the Centers for Disease Control and Prevention, Atlanta, wrote that these findings provide solid evidence that reducing antibiotic use can lead to a decrease in resistant pneumococcal infections. “The challenge now is for clinicians to reduce unnecessary use” of antibiotics, they wrote (J. Infect. Dis. 2008;197:1082-3).

The researchers reviewed all 236,466 prescriptions for oral antibiotics written during 1999-2003 for children aged younger than 5 years in seven large pediatric primary care clinics. Five of these were in urban Jewish centers and two in Bedouin townships. There was a 24% drop in the prescription rate during the warm months, compared with the cold months. The mean monthly antibiotic prescription rate was 291 per 1,000 children in the winter and 222 per 1,000 in the summer. Rates of antibiotic resistance showed a corresponding seasonal variation.

Although this pattern was seen in both populations, the urban Jewish population showed a much more pronounced—and statistically significant—seasonal variation in both prescribing rates and resistance rates than did the rural Bedouin population.

In the Jewish population, the rate of penicillin resistance was 43% in the cold months, compared with 29% in the warm months. The rate of erythromycin resistance was 29% in the cold months, compared with 20% in the warm months. And the rate of multidrug resistance was 25% in the cold months, compared with 15%. The differences were smaller and not statistically significant in Bedouin children.

These findings suggest that interventions to reduce antibiotic overuse “may reduce resistance in the community faster than previously thought,” they added.

The rates at which oral antibiotics were prescribed to children under age 5 years were directly related to the rates of resistant Streptococcus pneumoniae cultured from acute otitis media cases in a study reviewing more than 200,000 prescriptions.

In two distinct populations in southern Israel that were followed for 5 successive years, a “remarkable” seasonal reduction in antibiotic prescriptions during the warm months was significantly associated with a marked reduction in antibiotic resistance rates in pneumococcal isolates, said Dr. Ron Dagan of Soroka University Medical Center, Beer-Sheva, Israel, and his associates (J. Infect. Dis. 2008;197:1094-102).

“In Jewish children, each monthly increase in 10 prescriptions per 1,000 children was associated with a 1.05-fold increase in the odds of penicillin resistance during that month. The corresponding odds ratio for erythromycin resistance was 1.04, and for multidrug resistance it was 1.04,” they wrote.

In an accompanying editorial, Dr. Cindy R. Friedman and Dr. Cynthia G. Whitney of the Centers for Disease Control and Prevention, Atlanta, wrote that these findings provide solid evidence that reducing antibiotic use can lead to a decrease in resistant pneumococcal infections. “The challenge now is for clinicians to reduce unnecessary use” of antibiotics, they wrote (J. Infect. Dis. 2008;197:1082-3).

The researchers reviewed all 236,466 prescriptions for oral antibiotics written during 1999-2003 for children aged younger than 5 years in seven large pediatric primary care clinics. Five of these were in urban Jewish centers and two in Bedouin townships. There was a 24% drop in the prescription rate during the warm months, compared with the cold months. The mean monthly antibiotic prescription rate was 291 per 1,000 children in the winter and 222 per 1,000 in the summer. Rates of antibiotic resistance showed a corresponding seasonal variation.

Although this pattern was seen in both populations, the urban Jewish population showed a much more pronounced—and statistically significant—seasonal variation in both prescribing rates and resistance rates than did the rural Bedouin population.

In the Jewish population, the rate of penicillin resistance was 43% in the cold months, compared with 29% in the warm months. The rate of erythromycin resistance was 29% in the cold months, compared with 20% in the warm months. And the rate of multidrug resistance was 25% in the cold months, compared with 15%. The differences were smaller and not statistically significant in Bedouin children.

These findings suggest that interventions to reduce antibiotic overuse “may reduce resistance in the community faster than previously thought,” they added.

Statins reduced systolic and diastolic blood pressure, even in normotensive subjects and those with “prehypertension,” in a secondary analysis of data collected in the University of California, San Diego, Statin Study.

Both simvastatin, the most lipophilic statin, and pravastatin, the most hydrophilic statin, were found to decrease blood pressure “substantially, although the mean absolute magnitude of the change was modest in this largely nonhypertensive sample receiving relatively low statin dosages,” Dr. Beatrice A. Golomb and her associates at the university reported based on their analysis.

The investigators used data from the large 6-month UCSD Statin Study to assess the impact of the anticholesterol drugs on blood pressure because data from many small studies have suggested that statins improve hypertension.

However, these studies “have been correlational, uncontrolled, tested against other active drugs with uncertain impact on BP, unblinded, nonrandomized, or without assessment of statistical significance,” they noted.

In contrast, the UCSD Statin Study randomly assigned 973 participants (about 68% men) to 20 mg/day simvastatin, 40 mg/day pravastatin, or placebo in a double-blind fashion and assessed several factors, including blood pressure, at 1 month and 6 months, as well as at 2 months after the study was completed.

Blood pressure level was not a primary end point of the initial analysis.

The mean age of the placebo patients was nearly 58 years; the treated patient mean was nearly 57 years. More than 80% of the patients were white.

In the secondary analysis by Dr. Golomb and her associates, all of the participants, regardless of their blood pressure status at baseline, showed reductions in systolic and diastolic pressure after 1 month of statin treatment, though the difference between active therapy and placebo was nonsignificant at that point.

By 6 months, the participants in both of the statin groups showed significant reductions in blood pressure, compared with participants in the placebo group.

For both drugs, the reductions in blood pressure ranged from 2.4 to 2.8 mm Hg for both systolic and diastolic blood pressure.

However, these differences had dissipated at follow-up assessment 2 months after the treatment was discontinued, reported Dr. Golomb and her associates (Arch. Intern. Med. 2008;168:721-7).

Statin-induced decreases in blood pressure, although they might be “modest,” may well “contribute to reductions in transient ischemic attacks and stroke” that have been reported with statin therapy, they added.

Participants who had normal blood pressure, as well as those with “prehypertension,” showed declines in blood pressure similar to those seen with hypertension, according to the findings of the analysis.

This refutes the findings of a previous study in which researchers suggested that statins decrease only high blood pressure, the investigators noted.

The current study excluded participants who had diabetes, known cardiovascular disease, and very high or very low LDL cholesterol levels, so the findings might not extend to those groups, the researchers added.

Statins reduced systolic and diastolic blood pressure, even in normotensive subjects and those with “prehypertension,” in a secondary analysis of data collected in the University of California, San Diego, Statin Study.

Both simvastatin, the most lipophilic statin, and pravastatin, the most hydrophilic statin, were found to decrease blood pressure “substantially, although the mean absolute magnitude of the change was modest in this largely nonhypertensive sample receiving relatively low statin dosages,” Dr. Beatrice A. Golomb and her associates at the university reported based on their analysis.

The investigators used data from the large 6-month UCSD Statin Study to assess the impact of the anticholesterol drugs on blood pressure because data from many small studies have suggested that statins improve hypertension.

However, these studies “have been correlational, uncontrolled, tested against other active drugs with uncertain impact on BP, unblinded, nonrandomized, or without assessment of statistical significance,” they noted.

In contrast, the UCSD Statin Study randomly assigned 973 participants (about 68% men) to 20 mg/day simvastatin, 40 mg/day pravastatin, or placebo in a double-blind fashion and assessed several factors, including blood pressure, at 1 month and 6 months, as well as at 2 months after the study was completed.

Blood pressure level was not a primary end point of the initial analysis.

The mean age of the placebo patients was nearly 58 years; the treated patient mean was nearly 57 years. More than 80% of the patients were white.

In the secondary analysis by Dr. Golomb and her associates, all of the participants, regardless of their blood pressure status at baseline, showed reductions in systolic and diastolic pressure after 1 month of statin treatment, though the difference between active therapy and placebo was nonsignificant at that point.

By 6 months, the participants in both of the statin groups showed significant reductions in blood pressure, compared with participants in the placebo group.

For both drugs, the reductions in blood pressure ranged from 2.4 to 2.8 mm Hg for both systolic and diastolic blood pressure.

However, these differences had dissipated at follow-up assessment 2 months after the treatment was discontinued, reported Dr. Golomb and her associates (Arch. Intern. Med. 2008;168:721-7).

Statin-induced decreases in blood pressure, although they might be “modest,” may well “contribute to reductions in transient ischemic attacks and stroke” that have been reported with statin therapy, they added.

Participants who had normal blood pressure, as well as those with “prehypertension,” showed declines in blood pressure similar to those seen with hypertension, according to the findings of the analysis.

This refutes the findings of a previous study in which researchers suggested that statins decrease only high blood pressure, the investigators noted.

The current study excluded participants who had diabetes, known cardiovascular disease, and very high or very low LDL cholesterol levels, so the findings might not extend to those groups, the researchers added.

Statins reduced systolic and diastolic blood pressure, even in normotensive subjects and those with “prehypertension,” in a secondary analysis of data collected in the University of California, San Diego, Statin Study.

Both simvastatin, the most lipophilic statin, and pravastatin, the most hydrophilic statin, were found to decrease blood pressure “substantially, although the mean absolute magnitude of the change was modest in this largely nonhypertensive sample receiving relatively low statin dosages,” Dr. Beatrice A. Golomb and her associates at the university reported based on their analysis.

The investigators used data from the large 6-month UCSD Statin Study to assess the impact of the anticholesterol drugs on blood pressure because data from many small studies have suggested that statins improve hypertension.

However, these studies “have been correlational, uncontrolled, tested against other active drugs with uncertain impact on BP, unblinded, nonrandomized, or without assessment of statistical significance,” they noted.

In contrast, the UCSD Statin Study randomly assigned 973 participants (about 68% men) to 20 mg/day simvastatin, 40 mg/day pravastatin, or placebo in a double-blind fashion and assessed several factors, including blood pressure, at 1 month and 6 months, as well as at 2 months after the study was completed.

Blood pressure level was not a primary end point of the initial analysis.

The mean age of the placebo patients was nearly 58 years; the treated patient mean was nearly 57 years. More than 80% of the patients were white.

In the secondary analysis by Dr. Golomb and her associates, all of the participants, regardless of their blood pressure status at baseline, showed reductions in systolic and diastolic pressure after 1 month of statin treatment, though the difference between active therapy and placebo was nonsignificant at that point.

By 6 months, the participants in both of the statin groups showed significant reductions in blood pressure, compared with participants in the placebo group.

For both drugs, the reductions in blood pressure ranged from 2.4 to 2.8 mm Hg for both systolic and diastolic blood pressure.

However, these differences had dissipated at follow-up assessment 2 months after the treatment was discontinued, reported Dr. Golomb and her associates (Arch. Intern. Med. 2008;168:721-7).

Statin-induced decreases in blood pressure, although they might be “modest,” may well “contribute to reductions in transient ischemic attacks and stroke” that have been reported with statin therapy, they added.

Participants who had normal blood pressure, as well as those with “prehypertension,” showed declines in blood pressure similar to those seen with hypertension, according to the findings of the analysis.

This refutes the findings of a previous study in which researchers suggested that statins decrease only high blood pressure, the investigators noted.

The current study excluded participants who had diabetes, known cardiovascular disease, and very high or very low LDL cholesterol levels, so the findings might not extend to those groups, the researchers added.

Female sex, exposure to prenatal corticosteroid therapy, singleton birth, and increased birth weight (in 100-g increments) each improve an infant's chances of a positive outcome with intensive care.

The magnitude of the benefit is similar to that of an extra week of gestational age, Dr. Jon E. Tyson and his associates at the National Institute of Child Health and Human Development (NICHD) wrote in the April 17 New England Journal of Medicine.

Decisions about admitting extremely premature infants to intensive care are “highly controversial,” with most centers in the United States selecting patients solely on the basis of gestational age thresholds. “Such care is likely to be routinely administered at 25 weeks' gestation but may be provided only with parental agreement at 23–24 weeks, and only 'comfort care' may be given at 22 weeks,” the investigators noted.

The researchers assessed a cohort of 4,446 infants born at 22–25 weeks' gestation at 19 medical centers in the NICHD's neonatal research network between 1998 and 2004. At a corrected age of 18–22 months, 49% of the study subjects had died, and 61% had died or sustained profound impairment.

Factors that might contribute to outcome were examined, and the four listed above were found to significantly improve the rates of survival and survival without impairment. The improvements were equivalent to a 1-week increase in gestational age, said Dr. Tyson of the University of Texas at Houston and associates.

“For example, among infants born midway between 24 and 25 completed weeks of gestation, the estimated likelihood of death or profound impairment was 33% for a 750-g, appropriate-for-gestational-age female singleton who received prenatal corticosteroids, but 87% for a 525-g, small-for-gestational-age male twin who did not receive prenatal corticosteroids,” they wrote.

Even among the highest-risk infants—those born before 24 weeks with a birth weight of 600 g or less—outcomes varied considerably according to these four risk factors. The maximum potential rate of survival without profound impairment was as low as 5% for boys weighing 401–500 g born at 22 weeks, but as high as 38% for girls weighing 501–600 g born at 24 weeks (N.Engl. J. Med;358:1672–81).

Nevertheless, in actual practice it turned out that girls were less likely than boys and that singletons were less likely than multiples to receive intensive care when they had the same likelihood of a favorable outcome.

Weighing the additional four factors into the decision “is likely to promote treatment decisions that are less arbitrary, more individualized, more transparent, and better justified than decisions based solely on gestational-age thresholds,” the investigators said.

To assist physicians faced with such decisions, the authors provided a Web-based tool (www.nichd.nih.gov/neonatalestimates

Dr. Tyson and associates added that in assessing outcomes, they included factors such as treatment cost, resource use, parental distress, and “infant suffering due to painful procedures, prolonged intubation, and such complications as intracranial hemorrhage, necrotizing enterocolitis, and recurrent episodes of hypoxia.”

“Barring major therapeutic advances, our findings indicate that extending intensive care to all of the most immature infants would entail considerable suffering, resource use, and cost in order to benefit only a small proportion of infants,” they noted.

Female sex, exposure to prenatal corticosteroid therapy, singleton birth, and increased birth weight (in 100-g increments) each improve an infant's chances of a positive outcome with intensive care.

The magnitude of the benefit is similar to that of an extra week of gestational age, Dr. Jon E. Tyson and his associates at the National Institute of Child Health and Human Development (NICHD) wrote in the April 17 New England Journal of Medicine.

Decisions about admitting extremely premature infants to intensive care are “highly controversial,” with most centers in the United States selecting patients solely on the basis of gestational age thresholds. “Such care is likely to be routinely administered at 25 weeks' gestation but may be provided only with parental agreement at 23–24 weeks, and only 'comfort care' may be given at 22 weeks,” the investigators noted.

The researchers assessed a cohort of 4,446 infants born at 22–25 weeks' gestation at 19 medical centers in the NICHD's neonatal research network between 1998 and 2004. At a corrected age of 18–22 months, 49% of the study subjects had died, and 61% had died or sustained profound impairment.

Factors that might contribute to outcome were examined, and the four listed above were found to significantly improve the rates of survival and survival without impairment. The improvements were equivalent to a 1-week increase in gestational age, said Dr. Tyson of the University of Texas at Houston and associates.

“For example, among infants born midway between 24 and 25 completed weeks of gestation, the estimated likelihood of death or profound impairment was 33% for a 750-g, appropriate-for-gestational-age female singleton who received prenatal corticosteroids, but 87% for a 525-g, small-for-gestational-age male twin who did not receive prenatal corticosteroids,” they wrote.

Even among the highest-risk infants—those born before 24 weeks with a birth weight of 600 g or less—outcomes varied considerably according to these four risk factors. The maximum potential rate of survival without profound impairment was as low as 5% for boys weighing 401–500 g born at 22 weeks, but as high as 38% for girls weighing 501–600 g born at 24 weeks (N.Engl. J. Med;358:1672–81).

Nevertheless, in actual practice it turned out that girls were less likely than boys and that singletons were less likely than multiples to receive intensive care when they had the same likelihood of a favorable outcome.

Weighing the additional four factors into the decision “is likely to promote treatment decisions that are less arbitrary, more individualized, more transparent, and better justified than decisions based solely on gestational-age thresholds,” the investigators said.

To assist physicians faced with such decisions, the authors provided a Web-based tool (www.nichd.nih.gov/neonatalestimates

Dr. Tyson and associates added that in assessing outcomes, they included factors such as treatment cost, resource use, parental distress, and “infant suffering due to painful procedures, prolonged intubation, and such complications as intracranial hemorrhage, necrotizing enterocolitis, and recurrent episodes of hypoxia.”

“Barring major therapeutic advances, our findings indicate that extending intensive care to all of the most immature infants would entail considerable suffering, resource use, and cost in order to benefit only a small proportion of infants,” they noted.

Female sex, exposure to prenatal corticosteroid therapy, singleton birth, and increased birth weight (in 100-g increments) each improve an infant's chances of a positive outcome with intensive care.

The magnitude of the benefit is similar to that of an extra week of gestational age, Dr. Jon E. Tyson and his associates at the National Institute of Child Health and Human Development (NICHD) wrote in the April 17 New England Journal of Medicine.

Decisions about admitting extremely premature infants to intensive care are “highly controversial,” with most centers in the United States selecting patients solely on the basis of gestational age thresholds. “Such care is likely to be routinely administered at 25 weeks' gestation but may be provided only with parental agreement at 23–24 weeks, and only 'comfort care' may be given at 22 weeks,” the investigators noted.

The researchers assessed a cohort of 4,446 infants born at 22–25 weeks' gestation at 19 medical centers in the NICHD's neonatal research network between 1998 and 2004. At a corrected age of 18–22 months, 49% of the study subjects had died, and 61% had died or sustained profound impairment.

Factors that might contribute to outcome were examined, and the four listed above were found to significantly improve the rates of survival and survival without impairment. The improvements were equivalent to a 1-week increase in gestational age, said Dr. Tyson of the University of Texas at Houston and associates.

“For example, among infants born midway between 24 and 25 completed weeks of gestation, the estimated likelihood of death or profound impairment was 33% for a 750-g, appropriate-for-gestational-age female singleton who received prenatal corticosteroids, but 87% for a 525-g, small-for-gestational-age male twin who did not receive prenatal corticosteroids,” they wrote.

Even among the highest-risk infants—those born before 24 weeks with a birth weight of 600 g or less—outcomes varied considerably according to these four risk factors. The maximum potential rate of survival without profound impairment was as low as 5% for boys weighing 401–500 g born at 22 weeks, but as high as 38% for girls weighing 501–600 g born at 24 weeks (N.Engl. J. Med;358:1672–81).

Nevertheless, in actual practice it turned out that girls were less likely than boys and that singletons were less likely than multiples to receive intensive care when they had the same likelihood of a favorable outcome.

Weighing the additional four factors into the decision “is likely to promote treatment decisions that are less arbitrary, more individualized, more transparent, and better justified than decisions based solely on gestational-age thresholds,” the investigators said.

To assist physicians faced with such decisions, the authors provided a Web-based tool (www.nichd.nih.gov/neonatalestimates

Dr. Tyson and associates added that in assessing outcomes, they included factors such as treatment cost, resource use, parental distress, and “infant suffering due to painful procedures, prolonged intubation, and such complications as intracranial hemorrhage, necrotizing enterocolitis, and recurrent episodes of hypoxia.”

“Barring major therapeutic advances, our findings indicate that extending intensive care to all of the most immature infants would entail considerable suffering, resource use, and cost in order to benefit only a small proportion of infants,” they noted.

Men and women who were born preterm have lower reproduction rates than those born at term, and their reproductive success declines in tandem with their gestational age at birth, according to a population-based study of Norwegians.

Women born preterm also are at increased risk of delivering their own infants preterm, Dr. Geeta K. Swamy of Duke University Medical Center, Durham, N.C., and her associates said in the March 26 issue of JAMA.

The investigators used a “comprehensive, detailed, and highly accurate” medical registry of the long-term reproductive success of 1,167,506 people born in Norway from 1967 to 1976. Approximately 5% of cases were preterm and, as expected, infant and childhood mortality were higher in this group. For both men and women, reproduction appeared considerably lower for those born preterm, and appeared to directly increase until about 35 weeks of gestation. Among women born at 22–27 weeks' gestation, 25% subsequently reproduced, compared with 68% of women who had been born at term. Of men born at 22–27 weeks, 14% reproduced, compared with 50% of those born at term.

Women born preterm had a similar “dose-dependent” risk of delivering their own infants preterm. For women born at 22–27 weeks' gestation, the preterm birth rate was 14%; those born at 28–32 weeks had a preterm birth rate slightly higher than 9%, and those born at 33–36 weeks had a rate slightly lower than 9%. Women born at term had a 6% rate of delivering preterm.

Similar patterns were seen for fetal stillbirths and for infant mortality, the investigators said (JAMA 2008;299:1429–36).

Dr. Swamy and her associates speculated that “while biological factors may be at the root of the problem, interrelated social and economic stressors likely also diminish reproductive ability.”

Lingering medical or cognitive problems among survivors of preterm birth may account for difficulties finding a mate. Educational achievement was lower among adults born preterm, but could have resulted directly from preterm birth or more indirectly from being born into “a high-risk social setting with poor parental education and a high rate of unmarried parents,” the researchers said.

In an editorial comment accompanying this report, Dr. Melissa M. Adams and Dr. Wanda D. Barfield of the Centers for Disease Control and Prevention, Atlanta, said the findings “should be interpreted with caution” because “the majority of preterm infants have good health and good reproduction.” On the other hand, reproductive trends in Norway represent “a best-case scenario” given that country's homogeneous population and universal access to health care (JAMA 2008;299:1477–8).

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Men and women who were born preterm have lower reproduction rates than those born at term, and their reproductive success declines in tandem with their gestational age at birth, according to a population-based study of Norwegians.

Women born preterm also are at increased risk of delivering their own infants preterm, Dr. Geeta K. Swamy of Duke University Medical Center, Durham, N.C., and her associates said in the March 26 issue of JAMA.

The investigators used a “comprehensive, detailed, and highly accurate” medical registry of the long-term reproductive success of 1,167,506 people born in Norway from 1967 to 1976. Approximately 5% of cases were preterm and, as expected, infant and childhood mortality were higher in this group. For both men and women, reproduction appeared considerably lower for those born preterm, and appeared to directly increase until about 35 weeks of gestation. Among women born at 22–27 weeks' gestation, 25% subsequently reproduced, compared with 68% of women who had been born at term. Of men born at 22–27 weeks, 14% reproduced, compared with 50% of those born at term.

Women born preterm had a similar “dose-dependent” risk of delivering their own infants preterm. For women born at 22–27 weeks' gestation, the preterm birth rate was 14%; those born at 28–32 weeks had a preterm birth rate slightly higher than 9%, and those born at 33–36 weeks had a rate slightly lower than 9%. Women born at term had a 6% rate of delivering preterm.

Similar patterns were seen for fetal stillbirths and for infant mortality, the investigators said (JAMA 2008;299:1429–36).

Dr. Swamy and her associates speculated that “while biological factors may be at the root of the problem, interrelated social and economic stressors likely also diminish reproductive ability.”

Lingering medical or cognitive problems among survivors of preterm birth may account for difficulties finding a mate. Educational achievement was lower among adults born preterm, but could have resulted directly from preterm birth or more indirectly from being born into “a high-risk social setting with poor parental education and a high rate of unmarried parents,” the researchers said.

In an editorial comment accompanying this report, Dr. Melissa M. Adams and Dr. Wanda D. Barfield of the Centers for Disease Control and Prevention, Atlanta, said the findings “should be interpreted with caution” because “the majority of preterm infants have good health and good reproduction.” On the other hand, reproductive trends in Norway represent “a best-case scenario” given that country's homogeneous population and universal access to health care (JAMA 2008;299:1477–8).

ELSEVIER GLOBAL MEDICAL NEWS

Men and women who were born preterm have lower reproduction rates than those born at term, and their reproductive success declines in tandem with their gestational age at birth, according to a population-based study of Norwegians.

Women born preterm also are at increased risk of delivering their own infants preterm, Dr. Geeta K. Swamy of Duke University Medical Center, Durham, N.C., and her associates said in the March 26 issue of JAMA.

The investigators used a “comprehensive, detailed, and highly accurate” medical registry of the long-term reproductive success of 1,167,506 people born in Norway from 1967 to 1976. Approximately 5% of cases were preterm and, as expected, infant and childhood mortality were higher in this group. For both men and women, reproduction appeared considerably lower for those born preterm, and appeared to directly increase until about 35 weeks of gestation. Among women born at 22–27 weeks' gestation, 25% subsequently reproduced, compared with 68% of women who had been born at term. Of men born at 22–27 weeks, 14% reproduced, compared with 50% of those born at term.

Women born preterm had a similar “dose-dependent” risk of delivering their own infants preterm. For women born at 22–27 weeks' gestation, the preterm birth rate was 14%; those born at 28–32 weeks had a preterm birth rate slightly higher than 9%, and those born at 33–36 weeks had a rate slightly lower than 9%. Women born at term had a 6% rate of delivering preterm.

Similar patterns were seen for fetal stillbirths and for infant mortality, the investigators said (JAMA 2008;299:1429–36).

Dr. Swamy and her associates speculated that “while biological factors may be at the root of the problem, interrelated social and economic stressors likely also diminish reproductive ability.”

Lingering medical or cognitive problems among survivors of preterm birth may account for difficulties finding a mate. Educational achievement was lower among adults born preterm, but could have resulted directly from preterm birth or more indirectly from being born into “a high-risk social setting with poor parental education and a high rate of unmarried parents,” the researchers said.

In an editorial comment accompanying this report, Dr. Melissa M. Adams and Dr. Wanda D. Barfield of the Centers for Disease Control and Prevention, Atlanta, said the findings “should be interpreted with caution” because “the majority of preterm infants have good health and good reproduction.” On the other hand, reproductive trends in Norway represent “a best-case scenario” given that country's homogeneous population and universal access to health care (JAMA 2008;299:1477–8).

ELSEVIER GLOBAL MEDICAL NEWS