Mary Ann Moon

Enterovirus 71 infection that results in CNS involvement can induce long-term neurologic sequelae in children, including low intelligence and behavioral problems, reported Dr. Luan-Yin Chang of National Taiwan University Hospital, and associates.

Best known as a cause of benign hand-foot-and-mouth disease and of viral encephalitis, enterovirus 71 has caused several large outbreaks since 1975, including epidemics in Bulgaria, Hungary, and Southeast Asia. A massive outbreak in Taiwan in 1998 led infectious disease experts there to develop a management program, which reduced acute mortality but left lingering concerns about long-term sequelae. “The effect of the virus on subsequent neurodevelopment and cognitive function of the survivors is not known (unlike the effects of other forms of viral encephalitis),” the researchers said.

From 2003 to 2005, they assessed the neurodevelopment and cognitive function of 142 children who had been infected during the epidemic and had CNS involvement.

In an editorial comment accompanying the report, Dr. John F. Modlin noted that unlike other enteroviruses, “enterovirus 71 possesses a unique ability to invade the ventral brain stem, cerebellum, and spinal cord, producing a spectrum of serious neuromotor syndromes.”

Dr. Modlin suggested that the experience with EV71 may closely parallel that with poliomyelitis in the first half of the 20th century, and that past outbreaks in Asia may portend future outbreaks in North America and other regions that have been spared so far.

Among the 142 study subjects, 61 had experienced mild CNS involvement (aseptic meningitis) that produced headache and irritability but no altered consciousness or focal signs. Another 53 subjects had experienced severe CNS involvement, including encephalitis with altered level of consciousness, a polio-like syndrome with acute limb weakness and decreased reflex and muscle strength, or encephalomyelitis. The remaining 28 subjects had had severe CNS involvement and developed cardiopulmonary failure caused by medullary damage within 2–36 hours.

The subjects' age at onset of the infection ranged from 1 month to 14 years (median age 2 years); their age at follow-up assessment ranged from 1 to 20 years (median age 5 years).

All subjects with mild CNS involvement recovered fully. One with severe CNS involvement showed residual left facial nerve palsy, and 10 showed unilateral limb weakness and atrophy. In contrast, 21 (75%) of those with severe CNS involvement followed by cardiopulmonary failure showed these sequelae as well as dysphagia necessitating tube feeding, central hypoventilation requiring ventilator support, seizure, or psychomotor retardation.

Cognitive outcomes showed a similar pattern. Neurodevelopment and IQ were unaffected in all patients with mild CNS involvement, and were delayed in only one subject who had had severe CNS involvement alone. Subjects with CNS involvement alone showed deficits in verbal comprehension if they had been younger than 2 years when infected. In contrast, neurodevelopment and IQ were profoundly affected in most of those with severe CNS involvement plus cardiopulmonary failure.

Psychiatric sequelae may be noticed only when children start attending school, and only 47 of these subjects had started school at the time of this assessment. Six of them (13%) were diagnosed as having ADHD requiring medication and, in some cases, special education services. More severe learning and behavioral problems are likely to emerge as the subjects age, Dr. Chang and associates said (N. Engl. J. Med. 2007;356:1226–34).

These results show that children who develop CNS involvement with EV71 infection, particularly those who also develop cardiopulmonary failure, would benefit from early evaluation and intervention for cognitive and behavioral problems, they said.

In his editorial comment, Dr. Modlin, chair of pediatrics at Dartmouth Medical School, Hanover, N.H., said that the epidemiologic pattern, clinical disease, and pathologic features of EV71 all are strikingly similar to those of poliomyelitis. Both viruses cause outbreaks “in which acute, severe, and sometimes fatal neuromotor disease occurs as a rare manifestation of common infections, especially in infants and young children.”

Both viruses also “target gray matter in the spinal cord and brainstem, causing acute neuronal destruction and inflammation,” although EV71 appears to cause more extensive and severe CNS damage, he said (N. Engl. J. Med. 2007;356:1204–5). It would be presumptuous to predict that EV71 infection will behave like poliomyelitis and cause large, annual summertime outbreaks in the West. However, “it would also be foolish not to be better prepared than we are now,” Dr. Modlin noted.

Enterovirus 71 infection that results in CNS involvement can induce long-term neurologic sequelae in children, including low intelligence and behavioral problems, reported Dr. Luan-Yin Chang of National Taiwan University Hospital, and associates.

Best known as a cause of benign hand-foot-and-mouth disease and of viral encephalitis, enterovirus 71 has caused several large outbreaks since 1975, including epidemics in Bulgaria, Hungary, and Southeast Asia. A massive outbreak in Taiwan in 1998 led infectious disease experts there to develop a management program, which reduced acute mortality but left lingering concerns about long-term sequelae. “The effect of the virus on subsequent neurodevelopment and cognitive function of the survivors is not known (unlike the effects of other forms of viral encephalitis),” the researchers said.

From 2003 to 2005, they assessed the neurodevelopment and cognitive function of 142 children who had been infected during the epidemic and had CNS involvement.

In an editorial comment accompanying the report, Dr. John F. Modlin noted that unlike other enteroviruses, “enterovirus 71 possesses a unique ability to invade the ventral brain stem, cerebellum, and spinal cord, producing a spectrum of serious neuromotor syndromes.”

Dr. Modlin suggested that the experience with EV71 may closely parallel that with poliomyelitis in the first half of the 20th century, and that past outbreaks in Asia may portend future outbreaks in North America and other regions that have been spared so far.

Among the 142 study subjects, 61 had experienced mild CNS involvement (aseptic meningitis) that produced headache and irritability but no altered consciousness or focal signs. Another 53 subjects had experienced severe CNS involvement, including encephalitis with altered level of consciousness, a polio-like syndrome with acute limb weakness and decreased reflex and muscle strength, or encephalomyelitis. The remaining 28 subjects had had severe CNS involvement and developed cardiopulmonary failure caused by medullary damage within 2–36 hours.

The subjects' age at onset of the infection ranged from 1 month to 14 years (median age 2 years); their age at follow-up assessment ranged from 1 to 20 years (median age 5 years).

All subjects with mild CNS involvement recovered fully. One with severe CNS involvement showed residual left facial nerve palsy, and 10 showed unilateral limb weakness and atrophy. In contrast, 21 (75%) of those with severe CNS involvement followed by cardiopulmonary failure showed these sequelae as well as dysphagia necessitating tube feeding, central hypoventilation requiring ventilator support, seizure, or psychomotor retardation.

Cognitive outcomes showed a similar pattern. Neurodevelopment and IQ were unaffected in all patients with mild CNS involvement, and were delayed in only one subject who had had severe CNS involvement alone. Subjects with CNS involvement alone showed deficits in verbal comprehension if they had been younger than 2 years when infected. In contrast, neurodevelopment and IQ were profoundly affected in most of those with severe CNS involvement plus cardiopulmonary failure.

Psychiatric sequelae may be noticed only when children start attending school, and only 47 of these subjects had started school at the time of this assessment. Six of them (13%) were diagnosed as having ADHD requiring medication and, in some cases, special education services. More severe learning and behavioral problems are likely to emerge as the subjects age, Dr. Chang and associates said (N. Engl. J. Med. 2007;356:1226–34).

These results show that children who develop CNS involvement with EV71 infection, particularly those who also develop cardiopulmonary failure, would benefit from early evaluation and intervention for cognitive and behavioral problems, they said.

In his editorial comment, Dr. Modlin, chair of pediatrics at Dartmouth Medical School, Hanover, N.H., said that the epidemiologic pattern, clinical disease, and pathologic features of EV71 all are strikingly similar to those of poliomyelitis. Both viruses cause outbreaks “in which acute, severe, and sometimes fatal neuromotor disease occurs as a rare manifestation of common infections, especially in infants and young children.”

Both viruses also “target gray matter in the spinal cord and brainstem, causing acute neuronal destruction and inflammation,” although EV71 appears to cause more extensive and severe CNS damage, he said (N. Engl. J. Med. 2007;356:1204–5). It would be presumptuous to predict that EV71 infection will behave like poliomyelitis and cause large, annual summertime outbreaks in the West. However, “it would also be foolish not to be better prepared than we are now,” Dr. Modlin noted.

Enterovirus 71 infection that results in CNS involvement can induce long-term neurologic sequelae in children, including low intelligence and behavioral problems, reported Dr. Luan-Yin Chang of National Taiwan University Hospital, and associates.

Best known as a cause of benign hand-foot-and-mouth disease and of viral encephalitis, enterovirus 71 has caused several large outbreaks since 1975, including epidemics in Bulgaria, Hungary, and Southeast Asia. A massive outbreak in Taiwan in 1998 led infectious disease experts there to develop a management program, which reduced acute mortality but left lingering concerns about long-term sequelae. “The effect of the virus on subsequent neurodevelopment and cognitive function of the survivors is not known (unlike the effects of other forms of viral encephalitis),” the researchers said.

From 2003 to 2005, they assessed the neurodevelopment and cognitive function of 142 children who had been infected during the epidemic and had CNS involvement.

In an editorial comment accompanying the report, Dr. John F. Modlin noted that unlike other enteroviruses, “enterovirus 71 possesses a unique ability to invade the ventral brain stem, cerebellum, and spinal cord, producing a spectrum of serious neuromotor syndromes.”

Dr. Modlin suggested that the experience with EV71 may closely parallel that with poliomyelitis in the first half of the 20th century, and that past outbreaks in Asia may portend future outbreaks in North America and other regions that have been spared so far.

Among the 142 study subjects, 61 had experienced mild CNS involvement (aseptic meningitis) that produced headache and irritability but no altered consciousness or focal signs. Another 53 subjects had experienced severe CNS involvement, including encephalitis with altered level of consciousness, a polio-like syndrome with acute limb weakness and decreased reflex and muscle strength, or encephalomyelitis. The remaining 28 subjects had had severe CNS involvement and developed cardiopulmonary failure caused by medullary damage within 2–36 hours.

The subjects' age at onset of the infection ranged from 1 month to 14 years (median age 2 years); their age at follow-up assessment ranged from 1 to 20 years (median age 5 years).

All subjects with mild CNS involvement recovered fully. One with severe CNS involvement showed residual left facial nerve palsy, and 10 showed unilateral limb weakness and atrophy. In contrast, 21 (75%) of those with severe CNS involvement followed by cardiopulmonary failure showed these sequelae as well as dysphagia necessitating tube feeding, central hypoventilation requiring ventilator support, seizure, or psychomotor retardation.

Cognitive outcomes showed a similar pattern. Neurodevelopment and IQ were unaffected in all patients with mild CNS involvement, and were delayed in only one subject who had had severe CNS involvement alone. Subjects with CNS involvement alone showed deficits in verbal comprehension if they had been younger than 2 years when infected. In contrast, neurodevelopment and IQ were profoundly affected in most of those with severe CNS involvement plus cardiopulmonary failure.

Psychiatric sequelae may be noticed only when children start attending school, and only 47 of these subjects had started school at the time of this assessment. Six of them (13%) were diagnosed as having ADHD requiring medication and, in some cases, special education services. More severe learning and behavioral problems are likely to emerge as the subjects age, Dr. Chang and associates said (N. Engl. J. Med. 2007;356:1226–34).

These results show that children who develop CNS involvement with EV71 infection, particularly those who also develop cardiopulmonary failure, would benefit from early evaluation and intervention for cognitive and behavioral problems, they said.

In his editorial comment, Dr. Modlin, chair of pediatrics at Dartmouth Medical School, Hanover, N.H., said that the epidemiologic pattern, clinical disease, and pathologic features of EV71 all are strikingly similar to those of poliomyelitis. Both viruses cause outbreaks “in which acute, severe, and sometimes fatal neuromotor disease occurs as a rare manifestation of common infections, especially in infants and young children.”

Both viruses also “target gray matter in the spinal cord and brainstem, causing acute neuronal destruction and inflammation,” although EV71 appears to cause more extensive and severe CNS damage, he said (N. Engl. J. Med. 2007;356:1204–5). It would be presumptuous to predict that EV71 infection will behave like poliomyelitis and cause large, annual summertime outbreaks in the West. However, “it would also be foolish not to be better prepared than we are now,” Dr. Modlin noted.

The protection afforded by a single dose of the varicella vaccine steadily wanes over time, according to Dr. Sandra S. Chaves of the Centers for Disease Control and Prevention, Atlanta, and her associates.

A second vaccine dose could increase protection “by increasing the proportion of children with protective antibody titers and an improved cellular immune response,” they added.

Several small outbreaks of chickenpox have occurred in the United States, despite the success of the varicella vaccination program initiated in 1995. Investigations of these small outbreaks have not been sufficiently powered to definitively determine whether immunity wanes after vaccination, the researchers said.

To answer the question, Dr. Chaves and her associates examined 10 years of data from a community-based varicella surveillance program involving 300 child care centers, public and private schools, physicians' private practices, HMOs, and public health clinics in Antelope Valley, Calif. In the decade following the inception of the varicella vaccination program, 11,356 subjects in the surveillance area developed the disease, including 1,080 (9.5%) who developed “breakthrough” varicella after being vaccinated.

The proportion of varicella cases that occurred in vaccinated children steadily rose from 1% in 1996 to 18% in 2000 to 60% in 2004. In a parallel trend, the incidence of breakthrough cases steadily increased as the interval following vaccination lengthened. Incidence rose from 1.6 per 1,000 person-years at 1 year post vaccination to 9.0 per 1,000 person-years at 5 years post vaccination, to 20.4 per 1,000 person-years at 8 years post vaccination, and to 58.2 per 1,000 person-years at 9 years post vaccination. This dramatic rise occurred against a backdrop of a substantial (85%) decline in overall varicella cases, the investigators noted (N. Engl. J. Med. 2007;356:1121–9).

The pattern of disease distribution also changed in recent years. Before the vaccine program was implemented, 73% of cases occurred in children aged 6 years or younger, with a peak disease frequency at age 3–6 years. In 2004, 30% of cases occurred in children who were 6 years or younger. Disease frequency peaked at age 6–9 years in vaccinated children and at 9–12 years in unvaccinated children.

The frequency of severe, as opposed to mild, varicella infection similarly increased over time, rising from 18% in 1995–1998 to 31% in 2001–2004.

The frequency of severe disease also increased with patient age, regardless of vaccination status. Severe disease was seen in 22% of children aged 1–7 years who acquired varicella, compared with 44% of those who were aged 13 or older when they became infected.

When the severity data were analyzed according to time elapsed since vaccination, the severity of varicella was found to have increased as this interval lengthened. The frequency of severe disease doubled among patients who were vaccinated 5 or more years previously, compared with those who were vaccinated more recently.

ELSEVIER GLOBAL MEDICAL NEWS

The protection afforded by a single dose of the varicella vaccine steadily wanes over time, according to Dr. Sandra S. Chaves of the Centers for Disease Control and Prevention, Atlanta, and her associates.

A second vaccine dose could increase protection “by increasing the proportion of children with protective antibody titers and an improved cellular immune response,” they added.

Several small outbreaks of chickenpox have occurred in the United States, despite the success of the varicella vaccination program initiated in 1995. Investigations of these small outbreaks have not been sufficiently powered to definitively determine whether immunity wanes after vaccination, the researchers said.

To answer the question, Dr. Chaves and her associates examined 10 years of data from a community-based varicella surveillance program involving 300 child care centers, public and private schools, physicians' private practices, HMOs, and public health clinics in Antelope Valley, Calif. In the decade following the inception of the varicella vaccination program, 11,356 subjects in the surveillance area developed the disease, including 1,080 (9.5%) who developed “breakthrough” varicella after being vaccinated.

The proportion of varicella cases that occurred in vaccinated children steadily rose from 1% in 1996 to 18% in 2000 to 60% in 2004. In a parallel trend, the incidence of breakthrough cases steadily increased as the interval following vaccination lengthened. Incidence rose from 1.6 per 1,000 person-years at 1 year post vaccination to 9.0 per 1,000 person-years at 5 years post vaccination, to 20.4 per 1,000 person-years at 8 years post vaccination, and to 58.2 per 1,000 person-years at 9 years post vaccination. This dramatic rise occurred against a backdrop of a substantial (85%) decline in overall varicella cases, the investigators noted (N. Engl. J. Med. 2007;356:1121–9).

The pattern of disease distribution also changed in recent years. Before the vaccine program was implemented, 73% of cases occurred in children aged 6 years or younger, with a peak disease frequency at age 3–6 years. In 2004, 30% of cases occurred in children who were 6 years or younger. Disease frequency peaked at age 6–9 years in vaccinated children and at 9–12 years in unvaccinated children.

The frequency of severe, as opposed to mild, varicella infection similarly increased over time, rising from 18% in 1995–1998 to 31% in 2001–2004.

The frequency of severe disease also increased with patient age, regardless of vaccination status. Severe disease was seen in 22% of children aged 1–7 years who acquired varicella, compared with 44% of those who were aged 13 or older when they became infected.

When the severity data were analyzed according to time elapsed since vaccination, the severity of varicella was found to have increased as this interval lengthened. The frequency of severe disease doubled among patients who were vaccinated 5 or more years previously, compared with those who were vaccinated more recently.

ELSEVIER GLOBAL MEDICAL NEWS

The protection afforded by a single dose of the varicella vaccine steadily wanes over time, according to Dr. Sandra S. Chaves of the Centers for Disease Control and Prevention, Atlanta, and her associates.

A second vaccine dose could increase protection “by increasing the proportion of children with protective antibody titers and an improved cellular immune response,” they added.

Several small outbreaks of chickenpox have occurred in the United States, despite the success of the varicella vaccination program initiated in 1995. Investigations of these small outbreaks have not been sufficiently powered to definitively determine whether immunity wanes after vaccination, the researchers said.

To answer the question, Dr. Chaves and her associates examined 10 years of data from a community-based varicella surveillance program involving 300 child care centers, public and private schools, physicians' private practices, HMOs, and public health clinics in Antelope Valley, Calif. In the decade following the inception of the varicella vaccination program, 11,356 subjects in the surveillance area developed the disease, including 1,080 (9.5%) who developed “breakthrough” varicella after being vaccinated.

The proportion of varicella cases that occurred in vaccinated children steadily rose from 1% in 1996 to 18% in 2000 to 60% in 2004. In a parallel trend, the incidence of breakthrough cases steadily increased as the interval following vaccination lengthened. Incidence rose from 1.6 per 1,000 person-years at 1 year post vaccination to 9.0 per 1,000 person-years at 5 years post vaccination, to 20.4 per 1,000 person-years at 8 years post vaccination, and to 58.2 per 1,000 person-years at 9 years post vaccination. This dramatic rise occurred against a backdrop of a substantial (85%) decline in overall varicella cases, the investigators noted (N. Engl. J. Med. 2007;356:1121–9).

The pattern of disease distribution also changed in recent years. Before the vaccine program was implemented, 73% of cases occurred in children aged 6 years or younger, with a peak disease frequency at age 3–6 years. In 2004, 30% of cases occurred in children who were 6 years or younger. Disease frequency peaked at age 6–9 years in vaccinated children and at 9–12 years in unvaccinated children.

The frequency of severe, as opposed to mild, varicella infection similarly increased over time, rising from 18% in 1995–1998 to 31% in 2001–2004.

The frequency of severe disease also increased with patient age, regardless of vaccination status. Severe disease was seen in 22% of children aged 1–7 years who acquired varicella, compared with 44% of those who were aged 13 or older when they became infected.

When the severity data were analyzed according to time elapsed since vaccination, the severity of varicella was found to have increased as this interval lengthened. The frequency of severe disease doubled among patients who were vaccinated 5 or more years previously, compared with those who were vaccinated more recently.

ELSEVIER GLOBAL MEDICAL NEWS

Overweight and obese premenopausal women lost more weight and showed more favorable metabolic changes after 1 year on the Atkins diet than did those who followed the Zone, LEARN, or Ornish diets, investigators have reported.

Women who followed the high-protein, high-fat, low-carbohydrate Atkins diet also showed no adverse changes in triglycerides, HDL cholesterol, blood pressure, or insulin resistance, as feared by some critics.

Although questions remain about long-term effects and mechanisms of action, “physicians whose patients initiate a low-carbohydrate diet can be reassured that weight loss is likely to be at least as large as for any other dietary pattern and that the lipid effects are unlikely to be of immediate concern,” Christopher D. Gardner, Ph.D., and his associates in the A TO Z (Atkins, Traditional, Ornish, Zone) Weight Loss Study wrote in the journal of the American Medical Association.

They cautioned that the magnitude of weight loss was modest at best with all four diets, ranging from 2% to 5% of total weight, and the trajectories of weight loss during the 1-year study indicated that differences in weight loss among the diets would diminish over time.

Dr. Gardner and his associates of Stanford (Calif.) University conducted the A TO Z study to compare the effects of four well-known diets representing a spectrum of carbohydrate intake. The Atkins diet is very low in carbohydrates; the Zone diet is low in carbohydrates; the LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) diet, is high in carbohydrates; and the Ornish diet is very high in carbohydrates.

Subjects were 311 women aged 25–50 years, with body mass indices of 27–40 kg/m2, who were randomly assigned to read one of the four diet books and attend eight 1-hour weekly classes during which the books and diets were discussed by a dietitian, and to follow one of the diets. The attrition rate was about 20% and did not differ significantly between diets.

Total energy intake did not differ among the four groups either at baseline or at any point during follow-up, even though two diets (Zone and LEARN) called for caloric restriction and the other two did not. There was a modest increase in physical activity in all groups.

The mean weight loss at 1 year was 4.7 kg for the Atkins diet, 1.6 kg for the Zone diet, 2.2 kg for the LEARN diet, and 2.6 kg for the Ornish diet (JAMA 2007;297:969–77).

There were no significant differences among the groups in percentage of body fat or in waist-to-hip ratio, nor in fasting insulin or fasting glucose levels. The decrease in blood pressure levels paralleled that in weight, with the Atkins group showing slightly larger decreases than the other groups. Triglycerides and HDL cholesterol showed slightly more improvement in the Atkins group, but LDL cholesterol did not.

“The reported effects of the current study should be interpreted as resulting from the combination of macronutrient changes that occur when following low- vs. high-carbohydrate diets, not changes in carbohydrates alone. Greater satiety from the higher protein content of the Atkins diet may have contributed to the benefits observed for that group,” the authors noted.

Triglycerides and HDL cholesterol showed slightly more improvement in women in the Atkins group. Elsevier Global Medical News

Overweight and obese premenopausal women lost more weight and showed more favorable metabolic changes after 1 year on the Atkins diet than did those who followed the Zone, LEARN, or Ornish diets, investigators have reported.

Women who followed the high-protein, high-fat, low-carbohydrate Atkins diet also showed no adverse changes in triglycerides, HDL cholesterol, blood pressure, or insulin resistance, as feared by some critics.

Although questions remain about long-term effects and mechanisms of action, “physicians whose patients initiate a low-carbohydrate diet can be reassured that weight loss is likely to be at least as large as for any other dietary pattern and that the lipid effects are unlikely to be of immediate concern,” Christopher D. Gardner, Ph.D., and his associates in the A TO Z (Atkins, Traditional, Ornish, Zone) Weight Loss Study wrote in the journal of the American Medical Association.

They cautioned that the magnitude of weight loss was modest at best with all four diets, ranging from 2% to 5% of total weight, and the trajectories of weight loss during the 1-year study indicated that differences in weight loss among the diets would diminish over time.

Dr. Gardner and his associates of Stanford (Calif.) University conducted the A TO Z study to compare the effects of four well-known diets representing a spectrum of carbohydrate intake. The Atkins diet is very low in carbohydrates; the Zone diet is low in carbohydrates; the LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) diet, is high in carbohydrates; and the Ornish diet is very high in carbohydrates.

Subjects were 311 women aged 25–50 years, with body mass indices of 27–40 kg/m2, who were randomly assigned to read one of the four diet books and attend eight 1-hour weekly classes during which the books and diets were discussed by a dietitian, and to follow one of the diets. The attrition rate was about 20% and did not differ significantly between diets.

Total energy intake did not differ among the four groups either at baseline or at any point during follow-up, even though two diets (Zone and LEARN) called for caloric restriction and the other two did not. There was a modest increase in physical activity in all groups.

The mean weight loss at 1 year was 4.7 kg for the Atkins diet, 1.6 kg for the Zone diet, 2.2 kg for the LEARN diet, and 2.6 kg for the Ornish diet (JAMA 2007;297:969–77).

There were no significant differences among the groups in percentage of body fat or in waist-to-hip ratio, nor in fasting insulin or fasting glucose levels. The decrease in blood pressure levels paralleled that in weight, with the Atkins group showing slightly larger decreases than the other groups. Triglycerides and HDL cholesterol showed slightly more improvement in the Atkins group, but LDL cholesterol did not.

“The reported effects of the current study should be interpreted as resulting from the combination of macronutrient changes that occur when following low- vs. high-carbohydrate diets, not changes in carbohydrates alone. Greater satiety from the higher protein content of the Atkins diet may have contributed to the benefits observed for that group,” the authors noted.

Triglycerides and HDL cholesterol showed slightly more improvement in women in the Atkins group. Elsevier Global Medical News

Overweight and obese premenopausal women lost more weight and showed more favorable metabolic changes after 1 year on the Atkins diet than did those who followed the Zone, LEARN, or Ornish diets, investigators have reported.

Women who followed the high-protein, high-fat, low-carbohydrate Atkins diet also showed no adverse changes in triglycerides, HDL cholesterol, blood pressure, or insulin resistance, as feared by some critics.

Although questions remain about long-term effects and mechanisms of action, “physicians whose patients initiate a low-carbohydrate diet can be reassured that weight loss is likely to be at least as large as for any other dietary pattern and that the lipid effects are unlikely to be of immediate concern,” Christopher D. Gardner, Ph.D., and his associates in the A TO Z (Atkins, Traditional, Ornish, Zone) Weight Loss Study wrote in the journal of the American Medical Association.

They cautioned that the magnitude of weight loss was modest at best with all four diets, ranging from 2% to 5% of total weight, and the trajectories of weight loss during the 1-year study indicated that differences in weight loss among the diets would diminish over time.

Dr. Gardner and his associates of Stanford (Calif.) University conducted the A TO Z study to compare the effects of four well-known diets representing a spectrum of carbohydrate intake. The Atkins diet is very low in carbohydrates; the Zone diet is low in carbohydrates; the LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) diet, is high in carbohydrates; and the Ornish diet is very high in carbohydrates.

Subjects were 311 women aged 25–50 years, with body mass indices of 27–40 kg/m2, who were randomly assigned to read one of the four diet books and attend eight 1-hour weekly classes during which the books and diets were discussed by a dietitian, and to follow one of the diets. The attrition rate was about 20% and did not differ significantly between diets.

Total energy intake did not differ among the four groups either at baseline or at any point during follow-up, even though two diets (Zone and LEARN) called for caloric restriction and the other two did not. There was a modest increase in physical activity in all groups.

The mean weight loss at 1 year was 4.7 kg for the Atkins diet, 1.6 kg for the Zone diet, 2.2 kg for the LEARN diet, and 2.6 kg for the Ornish diet (JAMA 2007;297:969–77).

There were no significant differences among the groups in percentage of body fat or in waist-to-hip ratio, nor in fasting insulin or fasting glucose levels. The decrease in blood pressure levels paralleled that in weight, with the Atkins group showing slightly larger decreases than the other groups. Triglycerides and HDL cholesterol showed slightly more improvement in the Atkins group, but LDL cholesterol did not.

“The reported effects of the current study should be interpreted as resulting from the combination of macronutrient changes that occur when following low- vs. high-carbohydrate diets, not changes in carbohydrates alone. Greater satiety from the higher protein content of the Atkins diet may have contributed to the benefits observed for that group,” the authors noted.

Triglycerides and HDL cholesterol showed slightly more improvement in women in the Atkins group. Elsevier Global Medical News

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, Jesse C. Stewart, Ph.D., and his associates reported in the Archives of General Psychiatry.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. Dr. Stewart and his associates of the University of Pittsburgh assessed a wide range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change.

This suggests that depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33).

The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, such as autonomic nervous system dysfunction, hypothalamic-pituitary-adrenal axis dysregulation, inflammatory processes, and altered platelet function, they said.

A post-hoc analysis of the data showed that IMT worsening was associated with somatic-vegetative symptoms of depression such as fatigue, sleep disturbance, loss of appetite, and anhedonia, but not associated with more cognitive-affective depressive symptoms such as sadness, pessimism, discontent, or indecisiveness.

It is possible that this is attributable to a genuine physiologic link between the somatic-vegetative symptoms of depression and the process of atherosclerosis. However, it also is possible that older people such as the subjects in this study simply are more likely to report somatic-vegetative symptoms rather than emotional symptoms, the investigators noted.

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, Jesse C. Stewart, Ph.D., and his associates reported in the Archives of General Psychiatry.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. Dr. Stewart and his associates of the University of Pittsburgh assessed a wide range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change.

This suggests that depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33).

The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, such as autonomic nervous system dysfunction, hypothalamic-pituitary-adrenal axis dysregulation, inflammatory processes, and altered platelet function, they said.

A post-hoc analysis of the data showed that IMT worsening was associated with somatic-vegetative symptoms of depression such as fatigue, sleep disturbance, loss of appetite, and anhedonia, but not associated with more cognitive-affective depressive symptoms such as sadness, pessimism, discontent, or indecisiveness.

It is possible that this is attributable to a genuine physiologic link between the somatic-vegetative symptoms of depression and the process of atherosclerosis. However, it also is possible that older people such as the subjects in this study simply are more likely to report somatic-vegetative symptoms rather than emotional symptoms, the investigators noted.

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, Jesse C. Stewart, Ph.D., and his associates reported in the Archives of General Psychiatry.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. Dr. Stewart and his associates of the University of Pittsburgh assessed a wide range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change.

This suggests that depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33).

The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, such as autonomic nervous system dysfunction, hypothalamic-pituitary-adrenal axis dysregulation, inflammatory processes, and altered platelet function, they said.

A post-hoc analysis of the data showed that IMT worsening was associated with somatic-vegetative symptoms of depression such as fatigue, sleep disturbance, loss of appetite, and anhedonia, but not associated with more cognitive-affective depressive symptoms such as sadness, pessimism, discontent, or indecisiveness.

It is possible that this is attributable to a genuine physiologic link between the somatic-vegetative symptoms of depression and the process of atherosclerosis. However, it also is possible that older people such as the subjects in this study simply are more likely to report somatic-vegetative symptoms rather than emotional symptoms, the investigators noted.

The incidence of secondary neoplasms continues to rise steadily for at least 30 years after successful treatment of childhood acute lymphoblastic leukemia, a retrospective study showed.

Most of the late-developing secondary neoplasms are low-grade tumors such as meningioma and basal cell carcinoma, but the risk for high-grade tumors, especially carcinomas, still significantly exceeds the risk in the general population.

These findings highlight the need for continued careful follow-up of adult survivors of childhood acute lymphoblastic leukemia (ALL), Dr. Nobuko Hijiya of St. Jude Children's Research Hospital, Memphis, and her associates reported.

Previous research data has shown a low (1%–3%) incidence of secondary neoplasms for the first 10–15 years after childhood ALL. Data on the longer-term incidence “has been limited by relatively incomplete and short follow-up times.”

Dr. Hijiya and her associates reviewed the records of all 2,169 children who had achieved complete remission after treatment, in clinical trials at St. Jude between 1962 and 1998. The median follow-up was 19 years (range, 2–41 years) postdiagnosis, and the median subject age at last follow-up was 25 years (range, 6–53 years).

A total of 168 subjects (nearly 8%) developed a secondary neoplasm—45 of them after experiencing a relapse of ALL. Acute myeloid leukemia was most common in those who remained in remission, whereas basal cell carcinoma was most common in those whose ALL had relapsed.

In this patient population, risk of developing a high-grade tumor was more than twice as high as that in the general population. (JAMA 2007;297:1207–15). Incidence of secondary neoplasms was 4% at 15 years after remission was achieved, 5% at 20 years, and 11% at 30 years.

The incidence of secondary neoplasms continues to rise steadily for at least 30 years after successful treatment of childhood acute lymphoblastic leukemia, a retrospective study showed.

Most of the late-developing secondary neoplasms are low-grade tumors such as meningioma and basal cell carcinoma, but the risk for high-grade tumors, especially carcinomas, still significantly exceeds the risk in the general population.

These findings highlight the need for continued careful follow-up of adult survivors of childhood acute lymphoblastic leukemia (ALL), Dr. Nobuko Hijiya of St. Jude Children's Research Hospital, Memphis, and her associates reported.

Previous research data has shown a low (1%–3%) incidence of secondary neoplasms for the first 10–15 years after childhood ALL. Data on the longer-term incidence “has been limited by relatively incomplete and short follow-up times.”

Dr. Hijiya and her associates reviewed the records of all 2,169 children who had achieved complete remission after treatment, in clinical trials at St. Jude between 1962 and 1998. The median follow-up was 19 years (range, 2–41 years) postdiagnosis, and the median subject age at last follow-up was 25 years (range, 6–53 years).

A total of 168 subjects (nearly 8%) developed a secondary neoplasm—45 of them after experiencing a relapse of ALL. Acute myeloid leukemia was most common in those who remained in remission, whereas basal cell carcinoma was most common in those whose ALL had relapsed.

In this patient population, risk of developing a high-grade tumor was more than twice as high as that in the general population. (JAMA 2007;297:1207–15). Incidence of secondary neoplasms was 4% at 15 years after remission was achieved, 5% at 20 years, and 11% at 30 years.

The incidence of secondary neoplasms continues to rise steadily for at least 30 years after successful treatment of childhood acute lymphoblastic leukemia, a retrospective study showed.

Most of the late-developing secondary neoplasms are low-grade tumors such as meningioma and basal cell carcinoma, but the risk for high-grade tumors, especially carcinomas, still significantly exceeds the risk in the general population.

These findings highlight the need for continued careful follow-up of adult survivors of childhood acute lymphoblastic leukemia (ALL), Dr. Nobuko Hijiya of St. Jude Children's Research Hospital, Memphis, and her associates reported.

Previous research data has shown a low (1%–3%) incidence of secondary neoplasms for the first 10–15 years after childhood ALL. Data on the longer-term incidence “has been limited by relatively incomplete and short follow-up times.”

Dr. Hijiya and her associates reviewed the records of all 2,169 children who had achieved complete remission after treatment, in clinical trials at St. Jude between 1962 and 1998. The median follow-up was 19 years (range, 2–41 years) postdiagnosis, and the median subject age at last follow-up was 25 years (range, 6–53 years).

A total of 168 subjects (nearly 8%) developed a secondary neoplasm—45 of them after experiencing a relapse of ALL. Acute myeloid leukemia was most common in those who remained in remission, whereas basal cell carcinoma was most common in those whose ALL had relapsed.

In this patient population, risk of developing a high-grade tumor was more than twice as high as that in the general population. (JAMA 2007;297:1207–15). Incidence of secondary neoplasms was 4% at 15 years after remission was achieved, 5% at 20 years, and 11% at 30 years.

Port-wine stains treated with a pulsed dye laser—the preferred method of treatment—show significant redarkening years later, reported Dr. Menno Huikeshoven and associates at the University of Amsterdam.

"We recommend that before commencing pulsed dye laser therapy, all patients should be informed of the possibility of redarkening of the stain after treatment," the investigators said in the March 22 issue of the New England Journal of Medicine.

Until now, long-term follow-up data on the results of laser treatment have been scarce and limited to case reports and subjective questionnaires. In this study, Dr. Huikeshoven and associates used objective color measurements to assess treated areas on the face or neck, as well as normally pigmented areas on the contralateral side, in 51 patients who had been treated and similarly assessed in a prospective trial 10 years earlier.

The subjects also completed a questionnaire eliciting their subjective opinion of their treatment results. Their ages at long-term follow-up ranged from 12 to 42 years.

Only color of the lesions was assessed, not other characteristics such as size, surface structure, or degree of hypertrophy, the researchers noted.

The treated areas showed significant redarkening over time, although they remained lighter than they had been before treatment. Of the 51 subjects, 45 sought further pulsed dye laser therapy after their initial five treatments and assessment in the original study.

"It can be concluded that the positive effect of five treatments is not completely durable and that significant redarkening occurs at long-term follow-up," the investigators said (N. Engl. J. Med. 2007;356:1235–40).

Thirty subjects (59%) reported that they were satisfied with the results of treatment, and 21 (41%) reported they were not satisfied.

The subjects tended to underestimate the changes in color in their port wine stains over time, with only 18 (35%) reporting that they believed their stains had darkened. This is probably because the changes occurred slowly over many years.

This finding highlights the importance of using objective measurements to assess possible changes rather than patient or physician questionnaires, the investigators noted.

In a separate interview with SKIN & ALLERGY NEWS, Dr. Robert A. Weiss of the department of dermatology at the John Hopkins University, Baltimore, said, "I would still recommend the treatment to a patient. Even if there is a bit of recurrence, it is still worthwhile to treat," he said adding that patients can be treated again with the pulsed dye laser after redarkening of the stain to lighten it again. "New lasers have become available since thepatients in this study were treated a decade ago," Dr. Weiss said

The investigators stated that whether the new lasers reduce the incidence of redarkening over time "remains to be investigated."

ELSEVIER GLOBAL MEDICAL NEWS

Port-wine stains treated with a pulsed dye laser—the preferred method of treatment—show significant redarkening years later, reported Dr. Menno Huikeshoven and associates at the University of Amsterdam.

"We recommend that before commencing pulsed dye laser therapy, all patients should be informed of the possibility of redarkening of the stain after treatment," the investigators said in the March 22 issue of the New England Journal of Medicine.

Until now, long-term follow-up data on the results of laser treatment have been scarce and limited to case reports and subjective questionnaires. In this study, Dr. Huikeshoven and associates used objective color measurements to assess treated areas on the face or neck, as well as normally pigmented areas on the contralateral side, in 51 patients who had been treated and similarly assessed in a prospective trial 10 years earlier.

The subjects also completed a questionnaire eliciting their subjective opinion of their treatment results. Their ages at long-term follow-up ranged from 12 to 42 years.

Only color of the lesions was assessed, not other characteristics such as size, surface structure, or degree of hypertrophy, the researchers noted.

The treated areas showed significant redarkening over time, although they remained lighter than they had been before treatment. Of the 51 subjects, 45 sought further pulsed dye laser therapy after their initial five treatments and assessment in the original study.

"It can be concluded that the positive effect of five treatments is not completely durable and that significant redarkening occurs at long-term follow-up," the investigators said (N. Engl. J. Med. 2007;356:1235–40).

Thirty subjects (59%) reported that they were satisfied with the results of treatment, and 21 (41%) reported they were not satisfied.

The subjects tended to underestimate the changes in color in their port wine stains over time, with only 18 (35%) reporting that they believed their stains had darkened. This is probably because the changes occurred slowly over many years.

This finding highlights the importance of using objective measurements to assess possible changes rather than patient or physician questionnaires, the investigators noted.

In a separate interview with SKIN & ALLERGY NEWS, Dr. Robert A. Weiss of the department of dermatology at the John Hopkins University, Baltimore, said, "I would still recommend the treatment to a patient. Even if there is a bit of recurrence, it is still worthwhile to treat," he said adding that patients can be treated again with the pulsed dye laser after redarkening of the stain to lighten it again. "New lasers have become available since thepatients in this study were treated a decade ago," Dr. Weiss said

The investigators stated that whether the new lasers reduce the incidence of redarkening over time "remains to be investigated."

ELSEVIER GLOBAL MEDICAL NEWS

Port-wine stains treated with a pulsed dye laser—the preferred method of treatment—show significant redarkening years later, reported Dr. Menno Huikeshoven and associates at the University of Amsterdam.

"We recommend that before commencing pulsed dye laser therapy, all patients should be informed of the possibility of redarkening of the stain after treatment," the investigators said in the March 22 issue of the New England Journal of Medicine.

Until now, long-term follow-up data on the results of laser treatment have been scarce and limited to case reports and subjective questionnaires. In this study, Dr. Huikeshoven and associates used objective color measurements to assess treated areas on the face or neck, as well as normally pigmented areas on the contralateral side, in 51 patients who had been treated and similarly assessed in a prospective trial 10 years earlier.

The subjects also completed a questionnaire eliciting their subjective opinion of their treatment results. Their ages at long-term follow-up ranged from 12 to 42 years.

Only color of the lesions was assessed, not other characteristics such as size, surface structure, or degree of hypertrophy, the researchers noted.

The treated areas showed significant redarkening over time, although they remained lighter than they had been before treatment. Of the 51 subjects, 45 sought further pulsed dye laser therapy after their initial five treatments and assessment in the original study.

"It can be concluded that the positive effect of five treatments is not completely durable and that significant redarkening occurs at long-term follow-up," the investigators said (N. Engl. J. Med. 2007;356:1235–40).

Thirty subjects (59%) reported that they were satisfied with the results of treatment, and 21 (41%) reported they were not satisfied.

The subjects tended to underestimate the changes in color in their port wine stains over time, with only 18 (35%) reporting that they believed their stains had darkened. This is probably because the changes occurred slowly over many years.

This finding highlights the importance of using objective measurements to assess possible changes rather than patient or physician questionnaires, the investigators noted.

In a separate interview with SKIN & ALLERGY NEWS, Dr. Robert A. Weiss of the department of dermatology at the John Hopkins University, Baltimore, said, "I would still recommend the treatment to a patient. Even if there is a bit of recurrence, it is still worthwhile to treat," he said adding that patients can be treated again with the pulsed dye laser after redarkening of the stain to lighten it again. "New lasers have become available since thepatients in this study were treated a decade ago," Dr. Weiss said

The investigators stated that whether the new lasers reduce the incidence of redarkening over time "remains to be investigated."

ELSEVIER GLOBAL MEDICAL NEWS

The prevalence of human papillomavirus infection is estimated to be 27% in American girls and women aged 14–59, according to a study published in the Journal of the American Medical Association.

The investigators conducted what they described as the first study to provide an estimate of prevalent human papillomavirus (HPV) infection across a broad age range in a nationally representative sample tested in 2003–2004.

The aim of the study was to determine the prevaccine population-based prevalence of HPV infection, establishing a baseline against which the HPV vaccine's efficacy can be gauged. Data were drawn from a subsample of 1,921 girls and women who participated in the National Health and Nutrition Examination Survey, reported Dr. Eileen F. Dunne and her associates at the Centers for Disease Control and Prevention and the National Center for Health Statistics. The subjects collected their own cervicovaginal swab specimens at mobile examination centers, and HPV DNA was extracted from the specimens and typed. Twenty-seven percent of the subjects were found to be HPV positive, which corresponds to 25 million girls and women in the general population with prevalent HPV infection, the investigators said (JAMA 2007;297:813–9).

The HPV prevalence increased from age 14 through age 24, then gradually declined. It was highest—45%–-in subjects aged 20–24 years. When the analysis was restricted to sexually active girls and women, HPV prevalence was approximately 40% for ages 14–19, 50% for ages 20–24, 28% for ages 25–29, 27% for ages 30–39, 24% for ages 40–49, and 20% for ages 50–59.

The overall prevalences of high-risk HPV types 16 and 18 were low, at 1.5% and 0.8%, respectively.

The prevalence of human papillomavirus infection is estimated to be 27% in American girls and women aged 14–59, according to a study published in the Journal of the American Medical Association.

The investigators conducted what they described as the first study to provide an estimate of prevalent human papillomavirus (HPV) infection across a broad age range in a nationally representative sample tested in 2003–2004.

The aim of the study was to determine the prevaccine population-based prevalence of HPV infection, establishing a baseline against which the HPV vaccine's efficacy can be gauged. Data were drawn from a subsample of 1,921 girls and women who participated in the National Health and Nutrition Examination Survey, reported Dr. Eileen F. Dunne and her associates at the Centers for Disease Control and Prevention and the National Center for Health Statistics. The subjects collected their own cervicovaginal swab specimens at mobile examination centers, and HPV DNA was extracted from the specimens and typed. Twenty-seven percent of the subjects were found to be HPV positive, which corresponds to 25 million girls and women in the general population with prevalent HPV infection, the investigators said (JAMA 2007;297:813–9).

The HPV prevalence increased from age 14 through age 24, then gradually declined. It was highest—45%–-in subjects aged 20–24 years. When the analysis was restricted to sexually active girls and women, HPV prevalence was approximately 40% for ages 14–19, 50% for ages 20–24, 28% for ages 25–29, 27% for ages 30–39, 24% for ages 40–49, and 20% for ages 50–59.

The overall prevalences of high-risk HPV types 16 and 18 were low, at 1.5% and 0.8%, respectively.

The prevalence of human papillomavirus infection is estimated to be 27% in American girls and women aged 14–59, according to a study published in the Journal of the American Medical Association.

The investigators conducted what they described as the first study to provide an estimate of prevalent human papillomavirus (HPV) infection across a broad age range in a nationally representative sample tested in 2003–2004.

The aim of the study was to determine the prevaccine population-based prevalence of HPV infection, establishing a baseline against which the HPV vaccine's efficacy can be gauged. Data were drawn from a subsample of 1,921 girls and women who participated in the National Health and Nutrition Examination Survey, reported Dr. Eileen F. Dunne and her associates at the Centers for Disease Control and Prevention and the National Center for Health Statistics. The subjects collected their own cervicovaginal swab specimens at mobile examination centers, and HPV DNA was extracted from the specimens and typed. Twenty-seven percent of the subjects were found to be HPV positive, which corresponds to 25 million girls and women in the general population with prevalent HPV infection, the investigators said (JAMA 2007;297:813–9).

The HPV prevalence increased from age 14 through age 24, then gradually declined. It was highest—45%–-in subjects aged 20–24 years. When the analysis was restricted to sexually active girls and women, HPV prevalence was approximately 40% for ages 14–19, 50% for ages 20–24, 28% for ages 25–29, 27% for ages 30–39, 24% for ages 40–49, and 20% for ages 50–59.

The overall prevalences of high-risk HPV types 16 and 18 were low, at 1.5% and 0.8%, respectively.

CT screening dramatically raised the rate of detecting small lung cancers and boosted the frequency of resections by a factor of 10 but did not reduce mortality from the disease in a preliminary study.

These findings must be validated in larger randomized trials. Nevertheless, they “should raise doubts about the premise underpinning CT screening for lung cancer, and also raise concerns about its potential harms if pursued on a wide scale,” the study investigators wrote in the Journal of the American Medical Association (JAMA 2007;297:953–61).

Such CT screening “should be considered an experimental procedure, based on an uncorroborated premise” that fatal tumors can be detected while they are still localized and potentially curable. This conclusion flies in the face of widespread but unfounded claims that lung CT screening “saves lives” and should be covered by Medicare and other payers, Dr. Peter B. Bach of Memorial Sloan-Kettering Cancer Center, New York, and his associates noted.

They assessed the effect of CT screening using data from three separate studies conducted at the Istituto Tumori in Milan, Italy; the Mayo Clinic in Rochester, Minn.; and the Moffitt Cancer Center in Tampa, Fla. All 3,246 subjects had a history of smoking. They were screened and then followed for a median of 3.9 years.

The researchers calculated subjects' expected risks of a lung cancer diagnosis and of lung cancer death, based on statistical models widely used for that purpose.

“Far greater numbers” of subjects were diagnosed as having lung cancer by CT screening than would have been diagnosed without screening. When researchers considered the data from all three studies, 144 cases were diagnosed whereas only 44 cases were predicted by the statistical model, raising the rate of cancer diagnoses by a factor of 3.2, Dr. Bach and his associates said.

Based on CT findings, 109 lung cancer resections were performed, when only 10.9 were predicted by the model, raising the rate of surgery 10-fold.

However, “there was no evidence that CT screening reduced the risk of death due to lung cancer in any of the studies individually or combined.”

“There appears to be neither a meaningful reduction in the number of advanced cancers being diagnosed nor a reduction in the number of individuals who die of lung cancer,” the investigators said.

The 10-fold increase in resections served only to excise tumors that were unlikely to cause clinically significant disease or death. Such thoracic surgeries “may be insufficiently beneficial to justify the resulting morbidities,” given that postoperative mortality after lung cancer resection averages 5% per year in the United States, “and the frequency of serious complications ranges from 20% to 44%,” they added.

In an editorial comment accompanying this report, Dr. William C. Black of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. John A. Baron of Dartmouth Medical School, Hanover, N.H., said that these findings present a stark contrast to those of the I-ELCAP study (International Early Lung Cancer Action Program) published 6 months earlier (N. Engl. J. Med. 2006;355:1763–71). The I-ELCAP investigators concluded from their findings that CT screening in populations at risk for lung cancer could prevent 80% of lung cancer deaths.

The study by Bach et al. more directly addresses the population effect of CT screening than does the ELCAP study, Dr. Black and Dr. Baron commented (JAMA 2007;297:995–7).

CT screening dramatically raised the rate of detecting small lung cancers and boosted the frequency of resections by a factor of 10 but did not reduce mortality from the disease in a preliminary study.

These findings must be validated in larger randomized trials. Nevertheless, they “should raise doubts about the premise underpinning CT screening for lung cancer, and also raise concerns about its potential harms if pursued on a wide scale,” the study investigators wrote in the Journal of the American Medical Association (JAMA 2007;297:953–61).

Such CT screening “should be considered an experimental procedure, based on an uncorroborated premise” that fatal tumors can be detected while they are still localized and potentially curable. This conclusion flies in the face of widespread but unfounded claims that lung CT screening “saves lives” and should be covered by Medicare and other payers, Dr. Peter B. Bach of Memorial Sloan-Kettering Cancer Center, New York, and his associates noted.

They assessed the effect of CT screening using data from three separate studies conducted at the Istituto Tumori in Milan, Italy; the Mayo Clinic in Rochester, Minn.; and the Moffitt Cancer Center in Tampa, Fla. All 3,246 subjects had a history of smoking. They were screened and then followed for a median of 3.9 years.

The researchers calculated subjects' expected risks of a lung cancer diagnosis and of lung cancer death, based on statistical models widely used for that purpose.

“Far greater numbers” of subjects were diagnosed as having lung cancer by CT screening than would have been diagnosed without screening. When researchers considered the data from all three studies, 144 cases were diagnosed whereas only 44 cases were predicted by the statistical model, raising the rate of cancer diagnoses by a factor of 3.2, Dr. Bach and his associates said.

Based on CT findings, 109 lung cancer resections were performed, when only 10.9 were predicted by the model, raising the rate of surgery 10-fold.

However, “there was no evidence that CT screening reduced the risk of death due to lung cancer in any of the studies individually or combined.”

“There appears to be neither a meaningful reduction in the number of advanced cancers being diagnosed nor a reduction in the number of individuals who die of lung cancer,” the investigators said.

The 10-fold increase in resections served only to excise tumors that were unlikely to cause clinically significant disease or death. Such thoracic surgeries “may be insufficiently beneficial to justify the resulting morbidities,” given that postoperative mortality after lung cancer resection averages 5% per year in the United States, “and the frequency of serious complications ranges from 20% to 44%,” they added.

In an editorial comment accompanying this report, Dr. William C. Black of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. John A. Baron of Dartmouth Medical School, Hanover, N.H., said that these findings present a stark contrast to those of the I-ELCAP study (International Early Lung Cancer Action Program) published 6 months earlier (N. Engl. J. Med. 2006;355:1763–71). The I-ELCAP investigators concluded from their findings that CT screening in populations at risk for lung cancer could prevent 80% of lung cancer deaths.

The study by Bach et al. more directly addresses the population effect of CT screening than does the ELCAP study, Dr. Black and Dr. Baron commented (JAMA 2007;297:995–7).

CT screening dramatically raised the rate of detecting small lung cancers and boosted the frequency of resections by a factor of 10 but did not reduce mortality from the disease in a preliminary study.

These findings must be validated in larger randomized trials. Nevertheless, they “should raise doubts about the premise underpinning CT screening for lung cancer, and also raise concerns about its potential harms if pursued on a wide scale,” the study investigators wrote in the Journal of the American Medical Association (JAMA 2007;297:953–61).

Such CT screening “should be considered an experimental procedure, based on an uncorroborated premise” that fatal tumors can be detected while they are still localized and potentially curable. This conclusion flies in the face of widespread but unfounded claims that lung CT screening “saves lives” and should be covered by Medicare and other payers, Dr. Peter B. Bach of Memorial Sloan-Kettering Cancer Center, New York, and his associates noted.

They assessed the effect of CT screening using data from three separate studies conducted at the Istituto Tumori in Milan, Italy; the Mayo Clinic in Rochester, Minn.; and the Moffitt Cancer Center in Tampa, Fla. All 3,246 subjects had a history of smoking. They were screened and then followed for a median of 3.9 years.

The researchers calculated subjects' expected risks of a lung cancer diagnosis and of lung cancer death, based on statistical models widely used for that purpose.

“Far greater numbers” of subjects were diagnosed as having lung cancer by CT screening than would have been diagnosed without screening. When researchers considered the data from all three studies, 144 cases were diagnosed whereas only 44 cases were predicted by the statistical model, raising the rate of cancer diagnoses by a factor of 3.2, Dr. Bach and his associates said.

Based on CT findings, 109 lung cancer resections were performed, when only 10.9 were predicted by the model, raising the rate of surgery 10-fold.

However, “there was no evidence that CT screening reduced the risk of death due to lung cancer in any of the studies individually or combined.”

“There appears to be neither a meaningful reduction in the number of advanced cancers being diagnosed nor a reduction in the number of individuals who die of lung cancer,” the investigators said.

The 10-fold increase in resections served only to excise tumors that were unlikely to cause clinically significant disease or death. Such thoracic surgeries “may be insufficiently beneficial to justify the resulting morbidities,” given that postoperative mortality after lung cancer resection averages 5% per year in the United States, “and the frequency of serious complications ranges from 20% to 44%,” they added.

In an editorial comment accompanying this report, Dr. William C. Black of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. John A. Baron of Dartmouth Medical School, Hanover, N.H., said that these findings present a stark contrast to those of the I-ELCAP study (International Early Lung Cancer Action Program) published 6 months earlier (N. Engl. J. Med. 2006;355:1763–71). The I-ELCAP investigators concluded from their findings that CT screening in populations at risk for lung cancer could prevent 80% of lung cancer deaths.

The study by Bach et al. more directly addresses the population effect of CT screening than does the ELCAP study, Dr. Black and Dr. Baron commented (JAMA 2007;297:995–7).

A new, much more accurate clinical algorithm for predicting cardiovascular risk in women has been developed and validated by investigators in the Women's Health Study.

The new method reclassified approximately half of women who had been previously categorized as intermediate risk into either low-risk or high-risk categories. If the new algorithm were applied to a representative population of 100,000 U.S. women who are now considered to be at intermediate risk, it would recategorize 13,500 of them as low risk, 48,500 as low to moderate risk, 32,500 as moderate to high risk, and 5,400 as high risk, researchers reported.

“As 8–10 million U.S. women have an estimated 1-year risk between 5% and 20%, application of these data could have an immediate effect on cardiovascular prevention,” allowing more accurate targeting of statin and other therapies, wrote Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston, and his associates in the WHS.

The investigators used data on a subgroup of 16,400 healthy WHS subjects to assess which of 35 possible risk markers would best predict CV risk, then developed a model (model A) that included the nine most valuable predictors. Next, they modified the model to create a simplified version (model B) that would be more practical for clinical use. They tested the validity of both models in another subgroup of 8,158 WHS subjects.

During a median follow-up of 10 years, 504 CV events occurred in the first cohort and 262 occurred in the validation cohort.

With model A, 43% of women who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 681 reclassified subjects, all but 93 were placed into more accurate risk categories, based on their 10-year clinical outcomes.

Among subjects who did not have diabetes, approximately 50% who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 722 reclassified subjects, all but 2 were placed into more accurate risk categories (JAMA 2007;297:611–9).

Similar results were obtained using the simplified model B, which the researchers have termed the Reynolds Risk Score. For the 647 subjects without diabetes who were reclassified using model B, all but 6 were placed into more accurate risk categories, they said.

The Reynolds Risk Score uses these eight clinical markers to predict risk: age, systolic blood pressure, hemoglobin A_1c if the patient is diabetic, current smoking status, total and HDL cholesterol levels, high-sensitivity C-reactive protein, and parental history of MI before the age of 60.

“A user-friendly calculator for the Reynolds Risk Score can be freely accessed at www.reynoldsriskscore.org

Homocysteine, fibrinogen, soluble intercellular adhesion molecule 1, and creatinine measures did not add to the accuracy of risk prediction, nor did body mass index or exercise frequency, Dr. Ridker and his associates said.

The researchers cautioned that since the study subjects were predominantly white, well-educated women, these findings may not be generalizable to other populations.

A new, much more accurate clinical algorithm for predicting cardiovascular risk in women has been developed and validated by investigators in the Women's Health Study.

The new method reclassified approximately half of women who had been previously categorized as intermediate risk into either low-risk or high-risk categories. If the new algorithm were applied to a representative population of 100,000 U.S. women who are now considered to be at intermediate risk, it would recategorize 13,500 of them as low risk, 48,500 as low to moderate risk, 32,500 as moderate to high risk, and 5,400 as high risk, researchers reported.

“As 8–10 million U.S. women have an estimated 1-year risk between 5% and 20%, application of these data could have an immediate effect on cardiovascular prevention,” allowing more accurate targeting of statin and other therapies, wrote Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston, and his associates in the WHS.

The investigators used data on a subgroup of 16,400 healthy WHS subjects to assess which of 35 possible risk markers would best predict CV risk, then developed a model (model A) that included the nine most valuable predictors. Next, they modified the model to create a simplified version (model B) that would be more practical for clinical use. They tested the validity of both models in another subgroup of 8,158 WHS subjects.

During a median follow-up of 10 years, 504 CV events occurred in the first cohort and 262 occurred in the validation cohort.

With model A, 43% of women who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 681 reclassified subjects, all but 93 were placed into more accurate risk categories, based on their 10-year clinical outcomes.

Among subjects who did not have diabetes, approximately 50% who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 722 reclassified subjects, all but 2 were placed into more accurate risk categories (JAMA 2007;297:611–9).

Similar results were obtained using the simplified model B, which the researchers have termed the Reynolds Risk Score. For the 647 subjects without diabetes who were reclassified using model B, all but 6 were placed into more accurate risk categories, they said.

The Reynolds Risk Score uses these eight clinical markers to predict risk: age, systolic blood pressure, hemoglobin A_1c if the patient is diabetic, current smoking status, total and HDL cholesterol levels, high-sensitivity C-reactive protein, and parental history of MI before the age of 60.

“A user-friendly calculator for the Reynolds Risk Score can be freely accessed at www.reynoldsriskscore.org

Homocysteine, fibrinogen, soluble intercellular adhesion molecule 1, and creatinine measures did not add to the accuracy of risk prediction, nor did body mass index or exercise frequency, Dr. Ridker and his associates said.

The researchers cautioned that since the study subjects were predominantly white, well-educated women, these findings may not be generalizable to other populations.

A new, much more accurate clinical algorithm for predicting cardiovascular risk in women has been developed and validated by investigators in the Women's Health Study.

The new method reclassified approximately half of women who had been previously categorized as intermediate risk into either low-risk or high-risk categories. If the new algorithm were applied to a representative population of 100,000 U.S. women who are now considered to be at intermediate risk, it would recategorize 13,500 of them as low risk, 48,500 as low to moderate risk, 32,500 as moderate to high risk, and 5,400 as high risk, researchers reported.

“As 8–10 million U.S. women have an estimated 1-year risk between 5% and 20%, application of these data could have an immediate effect on cardiovascular prevention,” allowing more accurate targeting of statin and other therapies, wrote Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston, and his associates in the WHS.

The investigators used data on a subgroup of 16,400 healthy WHS subjects to assess which of 35 possible risk markers would best predict CV risk, then developed a model (model A) that included the nine most valuable predictors. Next, they modified the model to create a simplified version (model B) that would be more practical for clinical use. They tested the validity of both models in another subgroup of 8,158 WHS subjects.

During a median follow-up of 10 years, 504 CV events occurred in the first cohort and 262 occurred in the validation cohort.

With model A, 43% of women who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 681 reclassified subjects, all but 93 were placed into more accurate risk categories, based on their 10-year clinical outcomes.

Among subjects who did not have diabetes, approximately 50% who had been classified as being at intermediate risk by traditional criteria were reclassified as being at either lower or higher risk. Of these 722 reclassified subjects, all but 2 were placed into more accurate risk categories (JAMA 2007;297:611–9).

Similar results were obtained using the simplified model B, which the researchers have termed the Reynolds Risk Score. For the 647 subjects without diabetes who were reclassified using model B, all but 6 were placed into more accurate risk categories, they said.

The Reynolds Risk Score uses these eight clinical markers to predict risk: age, systolic blood pressure, hemoglobin A_1c if the patient is diabetic, current smoking status, total and HDL cholesterol levels, high-sensitivity C-reactive protein, and parental history of MI before the age of 60.

“A user-friendly calculator for the Reynolds Risk Score can be freely accessed at www.reynoldsriskscore.org

Homocysteine, fibrinogen, soluble intercellular adhesion molecule 1, and creatinine measures did not add to the accuracy of risk prediction, nor did body mass index or exercise frequency, Dr. Ridker and his associates said.

The researchers cautioned that since the study subjects were predominantly white, well-educated women, these findings may not be generalizable to other populations.

Adding rosiglitazone therapy to an insulin regimen appeared to be safe and to improve glycemic control in patients with type 2 diabetes in a study funded by the drug's manufacturer.

Rosiglitazone is one of the thiazolidinediones, “the newer insulin sensitizers” that improve β-cell function and prolong β-cell survival.

That result, in turn, enhances insulin sensitivity and improves glucose utilization, according to Dr. Ranjna Garg and associates at the Blackburn (England) Royal Infirmary's diabetes unit.

The first thiazolidinedione used in type 2 diabetes was troglitazone, a drug that was withdrawn from the market because of idiosyncratic reactions and sometimes fatal hepatic damage. Rosiglitazone has a different biochemical and metabolic profile and a lower incidence of hepatotoxicity, they said.

Dr. Garg and associates assessed its safety and efficacy in a 1-year open-label study of 53 patients who had inadequate glycemic control with insulin alone. The study was funded by GlaxoSmithKline.

Daily rosiglitazone reduced mean hemoglobin A_1c by a statistically significant 1.53%, from an average of 9.82% to an average of 8.29%.

“Tight glycemic control with reduction in HbA_1c by 1% is associated with reduction in diabetes-related end points by 21%, including death,” the investigators said (J. Diabetes Complications 2007;21:1–6).

The authors also noted, however, that the drug failed to reduce HbA_1c to target levels recommended by the American Diabetes Association.

Mean reduction in total insulin dose was 13.5%, which was not statistically significant. Twenty-eight patients were able to reduce their insulin dosage, and the remaining 25 were not.

Mean blood pressure improved significantly when rosiglitazone was added to insulin therapy.

There was no clinical hepatotoxicity during 12-month follow-up. Four patients discontinued the drug because of weight gain and another four because they perceived no benefit from therapy. Rosiglitazone was withdrawn in one additional patient because of fluid retention.

In addition to funding this study, GlaxoSmithKline has funded the diabetes unit at Blackburn Royal Infirmary and provided a travel grant to Dr. Garg. Dr. Garg's associate in this study, Dr. Geraint Rhys Jones, has been on the company's advisory board.

Adding rosiglitazone therapy to an insulin regimen appeared to be safe and to improve glycemic control in patients with type 2 diabetes in a study funded by the drug's manufacturer.

Rosiglitazone is one of the thiazolidinediones, “the newer insulin sensitizers” that improve β-cell function and prolong β-cell survival.

That result, in turn, enhances insulin sensitivity and improves glucose utilization, according to Dr. Ranjna Garg and associates at the Blackburn (England) Royal Infirmary's diabetes unit.

The first thiazolidinedione used in type 2 diabetes was troglitazone, a drug that was withdrawn from the market because of idiosyncratic reactions and sometimes fatal hepatic damage. Rosiglitazone has a different biochemical and metabolic profile and a lower incidence of hepatotoxicity, they said.

Dr. Garg and associates assessed its safety and efficacy in a 1-year open-label study of 53 patients who had inadequate glycemic control with insulin alone. The study was funded by GlaxoSmithKline.

Daily rosiglitazone reduced mean hemoglobin A_1c by a statistically significant 1.53%, from an average of 9.82% to an average of 8.29%.

“Tight glycemic control with reduction in HbA_1c by 1% is associated with reduction in diabetes-related end points by 21%, including death,” the investigators said (J. Diabetes Complications 2007;21:1–6).

The authors also noted, however, that the drug failed to reduce HbA_1c to target levels recommended by the American Diabetes Association.

Mean reduction in total insulin dose was 13.5%, which was not statistically significant. Twenty-eight patients were able to reduce their insulin dosage, and the remaining 25 were not.

Mean blood pressure improved significantly when rosiglitazone was added to insulin therapy.

There was no clinical hepatotoxicity during 12-month follow-up. Four patients discontinued the drug because of weight gain and another four because they perceived no benefit from therapy. Rosiglitazone was withdrawn in one additional patient because of fluid retention.

In addition to funding this study, GlaxoSmithKline has funded the diabetes unit at Blackburn Royal Infirmary and provided a travel grant to Dr. Garg. Dr. Garg's associate in this study, Dr. Geraint Rhys Jones, has been on the company's advisory board.

Adding rosiglitazone therapy to an insulin regimen appeared to be safe and to improve glycemic control in patients with type 2 diabetes in a study funded by the drug's manufacturer.

Rosiglitazone is one of the thiazolidinediones, “the newer insulin sensitizers” that improve β-cell function and prolong β-cell survival.

That result, in turn, enhances insulin sensitivity and improves glucose utilization, according to Dr. Ranjna Garg and associates at the Blackburn (England) Royal Infirmary's diabetes unit.

The first thiazolidinedione used in type 2 diabetes was troglitazone, a drug that was withdrawn from the market because of idiosyncratic reactions and sometimes fatal hepatic damage. Rosiglitazone has a different biochemical and metabolic profile and a lower incidence of hepatotoxicity, they said.

Dr. Garg and associates assessed its safety and efficacy in a 1-year open-label study of 53 patients who had inadequate glycemic control with insulin alone. The study was funded by GlaxoSmithKline.

Daily rosiglitazone reduced mean hemoglobin A_1c by a statistically significant 1.53%, from an average of 9.82% to an average of 8.29%.

“Tight glycemic control with reduction in HbA_1c by 1% is associated with reduction in diabetes-related end points by 21%, including death,” the investigators said (J. Diabetes Complications 2007;21:1–6).

The authors also noted, however, that the drug failed to reduce HbA_1c to target levels recommended by the American Diabetes Association.

Mean reduction in total insulin dose was 13.5%, which was not statistically significant. Twenty-eight patients were able to reduce their insulin dosage, and the remaining 25 were not.

Mean blood pressure improved significantly when rosiglitazone was added to insulin therapy.

There was no clinical hepatotoxicity during 12-month follow-up. Four patients discontinued the drug because of weight gain and another four because they perceived no benefit from therapy. Rosiglitazone was withdrawn in one additional patient because of fluid retention.

In addition to funding this study, GlaxoSmithKline has funded the diabetes unit at Blackburn Royal Infirmary and provided a travel grant to Dr. Garg. Dr. Garg's associate in this study, Dr. Geraint Rhys Jones, has been on the company's advisory board.