Mary Ann Moon

Major Finding: Obese adults and children residing with bariatric surgery patients showed significant reductions in weight, BMI, and waist circumference; improved eating habits; and increased physical activity during the year following the procedure.

Data Source: A prospective, 1-year study of weight and lifestyle changes among 35 bariatric surgery patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years.

Disclosures: This study was supported by the Medical Scholars Program at Stanford University. No financial conflicts of interest were reported.

Bariatric surgery appears to exert a favorable influence on family members of the recipient, leading to weight loss, healthier eating habits, and greater activity levels among adults and children residing with the patient, according to the results of a prospective, longitudinal study.

“Previous studies have shown that obesity may be a social contagion and that by associating with obese individuals, a person is more likely to become obese. Our study may demonstrate that bariatric surgery in selected populations can provide a reverse corollary and induce weight loss and healthy behaviors in people surrounding the patient,” according to Dr. Gavitt A. Woodard and her associates at Stanford (Calif.) University.

The investigators assessed weight and lifestyle changes in spouses, parents, and children who were residing with patients during the year after the patients underwent Roux-en-Y gastric bypass surgery. They enrolled 35 families, including 35 patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years during a 2-year period.

Both patients and family members were required to attend three preoperative educational sessions and five postoperative visits in which lifestyle modification was emphasized.

A high-protein, high-fiber, low-fat, low-sugar diet was recommended for the patients, which advised six small daily meals comprising 200-300 calories and including 4-6 ounces of protein.

Lifestyle modification included daily goals of increased physical activity (10,000 steps per day), 8 hours of sleep, moderation of alcohol intake, and avoidance of watching more than 2 hours of television.

After 1 year, the study subjects were evaluated by a physical examination as well as a battery of validated questionnaires assessing overall health, physical activity, sleep, risk behaviors, television viewing, alcohol consumption, and quality of life.

The gastric bypass patients lost weight as expected.

The mean weight of adult family members declined from 220 to 198 pounds, which was not statistically significant. However, when the family members were categorized by their own baseline weight, significant differences emerged.

Obese adult family members showed significant weight loss, from a mean of 234 to 226 pounds. Nonobese adult family members showed a nonsignificant weight loss from 180 to 176 pounds. This pattern held true for decreases in body mass index as well, Dr. Woodard and her associates wrote.

The pattern also was the same for waist circumference, with obese adult family members showing a significant decrease from a mean of 119 cm to 111 cm and nonobese adult family members showing no change in waist circumference.

According to these findings, obese adult family members lost 3% of their total weight in 1 year, which falls within the range of a 2%-5% weight loss reported for people following the Atkins, Zone, Ornish, or LEARN diets. “Living with a gastric bypass patient and undertaking a structured diet plan along with the patient may have an equivalent effect on weight,” the investigators said (Arch. Surg. 2011;146:1185-90).

Children were analyzed separately because of the expectation that their weight and waist circumference would increase because of natural growth.

Given the growth trajectories documented in their medical charts, obese children actually showed a smaller increase in BMI (29.6) than was expected (31.2). Nonobese children showed a slightly larger increase in BMI (19.8) than was expected (18.8).

As with the adult family members, children who were obese showed a significant reduction in waist circumference, from 119 cm to 111 cm, but nonobese children did not show any change in waist circumference.

Patients and their adult family members showed significant changes in their eating habits. Both groups had marked decreases in “uncontrolled eating” and in “emotional eating.” In addition, patients, but not their relatives, showed significantly increased “cognitive control of eating,” Dr. Woodard and her associates said.

However, children showed no changes in these measures. And neither adult family members nor children changed their food choices or decreased their intake of carbohydrates or junk food, while patients did achieve these goals, they reported.

Yet there was a significant increase in the percentage of children who reported that they were “on a diet,” from 25% at baseline to 50% at 1 year.

Patients and their adult family members reported significant declines in alcohol consumption, from 5 to 0.2 drinks per month among patients and from 11 to 0.8 drinks per month among adult family members.

Patients, adult relatives, and children all showed significant gains in daily activity levels. Children also decreased the amount of time they spent watching TV or using a computer every day, although this reduction did not reach statistical significance.

Overall, the study findings indicate that “bariatric surgery provides an opportunity for intervention for many individuals beyond the patient,” Dr. Woodard and her associates said.

Major Finding: Obese adults and children residing with bariatric surgery patients showed significant reductions in weight, BMI, and waist circumference; improved eating habits; and increased physical activity during the year following the procedure.

Data Source: A prospective, 1-year study of weight and lifestyle changes among 35 bariatric surgery patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years.

Disclosures: This study was supported by the Medical Scholars Program at Stanford University. No financial conflicts of interest were reported.

Bariatric surgery appears to exert a favorable influence on family members of the recipient, leading to weight loss, healthier eating habits, and greater activity levels among adults and children residing with the patient, according to the results of a prospective, longitudinal study.

“Previous studies have shown that obesity may be a social contagion and that by associating with obese individuals, a person is more likely to become obese. Our study may demonstrate that bariatric surgery in selected populations can provide a reverse corollary and induce weight loss and healthy behaviors in people surrounding the patient,” according to Dr. Gavitt A. Woodard and her associates at Stanford (Calif.) University.

The investigators assessed weight and lifestyle changes in spouses, parents, and children who were residing with patients during the year after the patients underwent Roux-en-Y gastric bypass surgery. They enrolled 35 families, including 35 patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years during a 2-year period.

Both patients and family members were required to attend three preoperative educational sessions and five postoperative visits in which lifestyle modification was emphasized.

A high-protein, high-fiber, low-fat, low-sugar diet was recommended for the patients, which advised six small daily meals comprising 200-300 calories and including 4-6 ounces of protein.

Lifestyle modification included daily goals of increased physical activity (10,000 steps per day), 8 hours of sleep, moderation of alcohol intake, and avoidance of watching more than 2 hours of television.

After 1 year, the study subjects were evaluated by a physical examination as well as a battery of validated questionnaires assessing overall health, physical activity, sleep, risk behaviors, television viewing, alcohol consumption, and quality of life.

The gastric bypass patients lost weight as expected.

The mean weight of adult family members declined from 220 to 198 pounds, which was not statistically significant. However, when the family members were categorized by their own baseline weight, significant differences emerged.

Obese adult family members showed significant weight loss, from a mean of 234 to 226 pounds. Nonobese adult family members showed a nonsignificant weight loss from 180 to 176 pounds. This pattern held true for decreases in body mass index as well, Dr. Woodard and her associates wrote.

The pattern also was the same for waist circumference, with obese adult family members showing a significant decrease from a mean of 119 cm to 111 cm and nonobese adult family members showing no change in waist circumference.

According to these findings, obese adult family members lost 3% of their total weight in 1 year, which falls within the range of a 2%-5% weight loss reported for people following the Atkins, Zone, Ornish, or LEARN diets. “Living with a gastric bypass patient and undertaking a structured diet plan along with the patient may have an equivalent effect on weight,” the investigators said (Arch. Surg. 2011;146:1185-90).

Children were analyzed separately because of the expectation that their weight and waist circumference would increase because of natural growth.

Given the growth trajectories documented in their medical charts, obese children actually showed a smaller increase in BMI (29.6) than was expected (31.2). Nonobese children showed a slightly larger increase in BMI (19.8) than was expected (18.8).

As with the adult family members, children who were obese showed a significant reduction in waist circumference, from 119 cm to 111 cm, but nonobese children did not show any change in waist circumference.

Patients and their adult family members showed significant changes in their eating habits. Both groups had marked decreases in “uncontrolled eating” and in “emotional eating.” In addition, patients, but not their relatives, showed significantly increased “cognitive control of eating,” Dr. Woodard and her associates said.

However, children showed no changes in these measures. And neither adult family members nor children changed their food choices or decreased their intake of carbohydrates or junk food, while patients did achieve these goals, they reported.

Yet there was a significant increase in the percentage of children who reported that they were “on a diet,” from 25% at baseline to 50% at 1 year.

Patients and their adult family members reported significant declines in alcohol consumption, from 5 to 0.2 drinks per month among patients and from 11 to 0.8 drinks per month among adult family members.

Patients, adult relatives, and children all showed significant gains in daily activity levels. Children also decreased the amount of time they spent watching TV or using a computer every day, although this reduction did not reach statistical significance.

Overall, the study findings indicate that “bariatric surgery provides an opportunity for intervention for many individuals beyond the patient,” Dr. Woodard and her associates said.

Major Finding: Obese adults and children residing with bariatric surgery patients showed significant reductions in weight, BMI, and waist circumference; improved eating habits; and increased physical activity during the year following the procedure.

Data Source: A prospective, 1-year study of weight and lifestyle changes among 35 bariatric surgery patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years.

Disclosures: This study was supported by the Medical Scholars Program at Stanford University. No financial conflicts of interest were reported.

Bariatric surgery appears to exert a favorable influence on family members of the recipient, leading to weight loss, healthier eating habits, and greater activity levels among adults and children residing with the patient, according to the results of a prospective, longitudinal study.

“Previous studies have shown that obesity may be a social contagion and that by associating with obese individuals, a person is more likely to become obese. Our study may demonstrate that bariatric surgery in selected populations can provide a reverse corollary and induce weight loss and healthy behaviors in people surrounding the patient,” according to Dr. Gavitt A. Woodard and her associates at Stanford (Calif.) University.

The investigators assessed weight and lifestyle changes in spouses, parents, and children who were residing with patients during the year after the patients underwent Roux-en-Y gastric bypass surgery. They enrolled 35 families, including 35 patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children younger than age 18 years during a 2-year period.

Both patients and family members were required to attend three preoperative educational sessions and five postoperative visits in which lifestyle modification was emphasized.

A high-protein, high-fiber, low-fat, low-sugar diet was recommended for the patients, which advised six small daily meals comprising 200-300 calories and including 4-6 ounces of protein.

Lifestyle modification included daily goals of increased physical activity (10,000 steps per day), 8 hours of sleep, moderation of alcohol intake, and avoidance of watching more than 2 hours of television.

After 1 year, the study subjects were evaluated by a physical examination as well as a battery of validated questionnaires assessing overall health, physical activity, sleep, risk behaviors, television viewing, alcohol consumption, and quality of life.

The gastric bypass patients lost weight as expected.

The mean weight of adult family members declined from 220 to 198 pounds, which was not statistically significant. However, when the family members were categorized by their own baseline weight, significant differences emerged.

Obese adult family members showed significant weight loss, from a mean of 234 to 226 pounds. Nonobese adult family members showed a nonsignificant weight loss from 180 to 176 pounds. This pattern held true for decreases in body mass index as well, Dr. Woodard and her associates wrote.

The pattern also was the same for waist circumference, with obese adult family members showing a significant decrease from a mean of 119 cm to 111 cm and nonobese adult family members showing no change in waist circumference.

According to these findings, obese adult family members lost 3% of their total weight in 1 year, which falls within the range of a 2%-5% weight loss reported for people following the Atkins, Zone, Ornish, or LEARN diets. “Living with a gastric bypass patient and undertaking a structured diet plan along with the patient may have an equivalent effect on weight,” the investigators said (Arch. Surg. 2011;146:1185-90).

Children were analyzed separately because of the expectation that their weight and waist circumference would increase because of natural growth.

Given the growth trajectories documented in their medical charts, obese children actually showed a smaller increase in BMI (29.6) than was expected (31.2). Nonobese children showed a slightly larger increase in BMI (19.8) than was expected (18.8).

As with the adult family members, children who were obese showed a significant reduction in waist circumference, from 119 cm to 111 cm, but nonobese children did not show any change in waist circumference.

Patients and their adult family members showed significant changes in their eating habits. Both groups had marked decreases in “uncontrolled eating” and in “emotional eating.” In addition, patients, but not their relatives, showed significantly increased “cognitive control of eating,” Dr. Woodard and her associates said.

However, children showed no changes in these measures. And neither adult family members nor children changed their food choices or decreased their intake of carbohydrates or junk food, while patients did achieve these goals, they reported.

Yet there was a significant increase in the percentage of children who reported that they were “on a diet,” from 25% at baseline to 50% at 1 year.

Patients and their adult family members reported significant declines in alcohol consumption, from 5 to 0.2 drinks per month among patients and from 11 to 0.8 drinks per month among adult family members.

Patients, adult relatives, and children all showed significant gains in daily activity levels. Children also decreased the amount of time they spent watching TV or using a computer every day, although this reduction did not reach statistical significance.

Overall, the study findings indicate that “bariatric surgery provides an opportunity for intervention for many individuals beyond the patient,” Dr. Woodard and her associates said.

Women with high-quality diets during the year before pregnancy were at lower risk than were those with poor diets for delivering a baby with orofacial clefts or neural tube defects, according to a study.

This finding, from an analysis of data in the ongoing National Birth Defects Prevention Study (NBDPS), is “notable” because previous analyses of the same data, “which assessed single-nutrient intakes in isolation, had not been informative.

“In particular, maternal intake of folic acid–containing vitamin/mineral supplements was not associated in the NBDPS with a reduced risk of neural tube defects, and findings for dietary folate were inconsistent” in these previous analyses, said Suzan L. Carmichael, Ph.D., of Stanford (Calif.) University and her associates.

“[Our] findings suggest that overall diet quality is more predictive of birth defect risk than intake of single nutrients,” they noted.

Dr. Carmichael and her colleagues developed two indexes of dietary quality, one modeled after the Mediterranean Diet Score and the second after the Diet Quality Index for Pregnancy. They then assessed how each of these indexes performed in predicting risk for isolated (nonsyndromic) neural tube defects and orofacial clefts using data on 9,558 pregnancies in the NBDPS.

The NBDPS is an ongoing multistate, population-based case-control study of well-defined birth defects. For this analysis, the researchers assessed 3,411 pregnancies involving isolated neural tube defects (936) or orofacial clefts (2,475), and 6,147 pregnancies that served as controls. All the deliveries occurred between 1997 and 2005.

For both indexes of dietary quality, “we observed reduced birth defects risks associated with higher dietary quality scores. That is, after adjusting for all covariates, increasing diet quality based on either index was associated with reduced risk of each birth defect studied,” the researchers said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.185]).

“The strongest associations were observed for anencephaly,” they added.

The findings were similar in further analyses of important subgroups of patients, including an assessment restricted to women who took vitamin/mineral supplements.

These results likely are generalizable to other women “because of [our] study's population-based design, active case ascertainment, and the racial/ethnic, geographic, and socioeconomic diversity” of the subjects.

“Although the focus on folic acid has enabled substantial reductions in the prevalence of neural tube defects and perhaps other birth defects, the population burden of birth defects remains extensive. If increased dietary quality can indeed have a greater impact than individual nutrients, appropriate public health messages may need to be developed that convey this broader perspective,” Dr. Carmichael and her associates said.

This study was supported in part by the National Institutes of Health and the Centers for Disease Control and Prevention. Dr. Carmichael and her associates reported no relevant financial disclosures.

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Eating Well Is the Best Defense

“The lesson from the article by Carmichael et al. is an important one: People, including women of childbearing age, should eat good food,” said David R. Jacobs Jr., Ph.D., and his associates.

“A nutrient [supplement] may correct a deficiency condition but not necessarily be of benefit at higher doses in well-nourished people,” they added.

“Reduction of neural tube defects may be achievable by diet alone, at the same time reducing potential risk for other chronic diseases in the rest of the population,” they said.

DR. JACOBS and his associates are in the division of epidemiology and community health at the University of Minnesota School of Public Health, Minneapolis. They reported no relevant financial disclosures. These remarks were taken from their editorial accompanying Dr. Carmichael's report (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.184]).

Women with high-quality diets during the year before pregnancy were at lower risk than were those with poor diets for delivering a baby with orofacial clefts or neural tube defects, according to a study.

This finding, from an analysis of data in the ongoing National Birth Defects Prevention Study (NBDPS), is “notable” because previous analyses of the same data, “which assessed single-nutrient intakes in isolation, had not been informative.

“In particular, maternal intake of folic acid–containing vitamin/mineral supplements was not associated in the NBDPS with a reduced risk of neural tube defects, and findings for dietary folate were inconsistent” in these previous analyses, said Suzan L. Carmichael, Ph.D., of Stanford (Calif.) University and her associates.

“[Our] findings suggest that overall diet quality is more predictive of birth defect risk than intake of single nutrients,” they noted.

Dr. Carmichael and her colleagues developed two indexes of dietary quality, one modeled after the Mediterranean Diet Score and the second after the Diet Quality Index for Pregnancy. They then assessed how each of these indexes performed in predicting risk for isolated (nonsyndromic) neural tube defects and orofacial clefts using data on 9,558 pregnancies in the NBDPS.

The NBDPS is an ongoing multistate, population-based case-control study of well-defined birth defects. For this analysis, the researchers assessed 3,411 pregnancies involving isolated neural tube defects (936) or orofacial clefts (2,475), and 6,147 pregnancies that served as controls. All the deliveries occurred between 1997 and 2005.

For both indexes of dietary quality, “we observed reduced birth defects risks associated with higher dietary quality scores. That is, after adjusting for all covariates, increasing diet quality based on either index was associated with reduced risk of each birth defect studied,” the researchers said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.185]).

“The strongest associations were observed for anencephaly,” they added.

The findings were similar in further analyses of important subgroups of patients, including an assessment restricted to women who took vitamin/mineral supplements.

These results likely are generalizable to other women “because of [our] study's population-based design, active case ascertainment, and the racial/ethnic, geographic, and socioeconomic diversity” of the subjects.

“Although the focus on folic acid has enabled substantial reductions in the prevalence of neural tube defects and perhaps other birth defects, the population burden of birth defects remains extensive. If increased dietary quality can indeed have a greater impact than individual nutrients, appropriate public health messages may need to be developed that convey this broader perspective,” Dr. Carmichael and her associates said.

This study was supported in part by the National Institutes of Health and the Centers for Disease Control and Prevention. Dr. Carmichael and her associates reported no relevant financial disclosures.

View on the News

Eating Well Is the Best Defense

“The lesson from the article by Carmichael et al. is an important one: People, including women of childbearing age, should eat good food,” said David R. Jacobs Jr., Ph.D., and his associates.

“A nutrient [supplement] may correct a deficiency condition but not necessarily be of benefit at higher doses in well-nourished people,” they added.

“Reduction of neural tube defects may be achievable by diet alone, at the same time reducing potential risk for other chronic diseases in the rest of the population,” they said.

DR. JACOBS and his associates are in the division of epidemiology and community health at the University of Minnesota School of Public Health, Minneapolis. They reported no relevant financial disclosures. These remarks were taken from their editorial accompanying Dr. Carmichael's report (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.184]).

Women with high-quality diets during the year before pregnancy were at lower risk than were those with poor diets for delivering a baby with orofacial clefts or neural tube defects, according to a study.

This finding, from an analysis of data in the ongoing National Birth Defects Prevention Study (NBDPS), is “notable” because previous analyses of the same data, “which assessed single-nutrient intakes in isolation, had not been informative.

“In particular, maternal intake of folic acid–containing vitamin/mineral supplements was not associated in the NBDPS with a reduced risk of neural tube defects, and findings for dietary folate were inconsistent” in these previous analyses, said Suzan L. Carmichael, Ph.D., of Stanford (Calif.) University and her associates.

“[Our] findings suggest that overall diet quality is more predictive of birth defect risk than intake of single nutrients,” they noted.

Dr. Carmichael and her colleagues developed two indexes of dietary quality, one modeled after the Mediterranean Diet Score and the second after the Diet Quality Index for Pregnancy. They then assessed how each of these indexes performed in predicting risk for isolated (nonsyndromic) neural tube defects and orofacial clefts using data on 9,558 pregnancies in the NBDPS.

The NBDPS is an ongoing multistate, population-based case-control study of well-defined birth defects. For this analysis, the researchers assessed 3,411 pregnancies involving isolated neural tube defects (936) or orofacial clefts (2,475), and 6,147 pregnancies that served as controls. All the deliveries occurred between 1997 and 2005.

For both indexes of dietary quality, “we observed reduced birth defects risks associated with higher dietary quality scores. That is, after adjusting for all covariates, increasing diet quality based on either index was associated with reduced risk of each birth defect studied,” the researchers said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.185]).

“The strongest associations were observed for anencephaly,” they added.

The findings were similar in further analyses of important subgroups of patients, including an assessment restricted to women who took vitamin/mineral supplements.

These results likely are generalizable to other women “because of [our] study's population-based design, active case ascertainment, and the racial/ethnic, geographic, and socioeconomic diversity” of the subjects.

“Although the focus on folic acid has enabled substantial reductions in the prevalence of neural tube defects and perhaps other birth defects, the population burden of birth defects remains extensive. If increased dietary quality can indeed have a greater impact than individual nutrients, appropriate public health messages may need to be developed that convey this broader perspective,” Dr. Carmichael and her associates said.

This study was supported in part by the National Institutes of Health and the Centers for Disease Control and Prevention. Dr. Carmichael and her associates reported no relevant financial disclosures.

View on the News

Eating Well Is the Best Defense

“The lesson from the article by Carmichael et al. is an important one: People, including women of childbearing age, should eat good food,” said David R. Jacobs Jr., Ph.D., and his associates.

“A nutrient [supplement] may correct a deficiency condition but not necessarily be of benefit at higher doses in well-nourished people,” they added.

“Reduction of neural tube defects may be achievable by diet alone, at the same time reducing potential risk for other chronic diseases in the rest of the population,” they said.

DR. JACOBS and his associates are in the division of epidemiology and community health at the University of Minnesota School of Public Health, Minneapolis. They reported no relevant financial disclosures. These remarks were taken from their editorial accompanying Dr. Carmichael's report (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.184]).

In-utero exposure to diethylstilbestrol was associated with a high lifetime risk of a broad spectrum of adverse outcomes in a follow-up study of patients now in their 40s, 50s, and 60s.

Most of these risks were increased by a factor of more than two, compared with the risks in women of the same age who were not exposed to diethylstilbestrol (DES), said Dr. Robert N. Hoover of the National Cancer Institute, Bethesda, Md., and his associates. “Although DES has not been prescribed for pregnant women in the United States for 40 years, adverse outcomes continue to occur in women exposed in utero, and continued monitoring … for established and unexpected adverse outcomes seems prudent,” they noted.

In the early 1990s, Dr. Hoover and his colleagues combined three cohort studies of DES-exposed women that had begun in the mid-1970s, so that the pooled subjects could be followed periodically with self-report questionnaires. Their Combined Cohort Study of DES Exposure involved 4,001 DES-exposed women and 1,683 nonexposed control subjects from the original cohorts, who were born between the late 1940s and the early 1960s and whose average age at last follow-up was 48 years.

Twelve adverse health outcomes that were significantly associated with DES in previous studies were assessed in the combined cohort, and all 12 were found to be significantly associated with DES in this combined analysis.

The hazard ratios (HRs) associated with DES exposure, compared with nonexposure, ranged from a low of 1.42 for preeclampsia to a high of 8.12 for neonatal death (usually related to preterm delivery). In ascending order, the HRs were 1.64 for spontaneous abortion; 1.82 for breast cancer diagnosed at age 40 or older; 2.28 for cervical intraepithelial neoplasia of grade 2 or higher; 2.35 for early menopause; 2.37 for infertility; 2.45 for stillbirth; 3.72 for ectopic pregnancy; 3.77 for loss of second-trimester pregnancy; and 4.68 for preterm delivery, the investigators wrote (N. Engl. J. Med. 2011;365:1304-14).

DES-exposed women who had clinical evidence of vaginal epithelial changes at a young age – a marker of high DES dose and exposure early in gestation – were found to have significantly higher risks for adverse outcomes than did exposed women who showed no vaginal epithelial changes. This finding provides additional support for the argument that DES exposure caused, and was not just linked to, the adverse outcomes, they said.

The researchers also calculated the excess risk of adverse outcomes that could be attributed directly to DES exposure. This excess risk was 1.7% for breast cancer, 3.4% for early menopause, 3.5% for CIN, 6.3% for stillbirth, 7.2% for neonatal death, 11.7% for both spontaneous abortion and ectopic pregnancy, 12.7% for preeclampsia, 14.7% for loss of second-trimester pregnancy, 17.8% for infertility, and 35.4% for preterm delivery.

The Combined Cohort Study of DES Exposure was supported by the National Cancer Institute. Dr. Robboy reports receiving consulting fees from UCB, Belgium. Dr. Karlan reports holding stock in and receiving board membership fees from IRIS International. Dr. Hatch receives royalties as a reviewer of the DES card on the UpToDate medical information site.

In-utero exposure to diethylstilbestrol was associated with a high lifetime risk of a broad spectrum of adverse outcomes in a follow-up study of patients now in their 40s, 50s, and 60s.

Most of these risks were increased by a factor of more than two, compared with the risks in women of the same age who were not exposed to diethylstilbestrol (DES), said Dr. Robert N. Hoover of the National Cancer Institute, Bethesda, Md., and his associates. “Although DES has not been prescribed for pregnant women in the United States for 40 years, adverse outcomes continue to occur in women exposed in utero, and continued monitoring … for established and unexpected adverse outcomes seems prudent,” they noted.

In the early 1990s, Dr. Hoover and his colleagues combined three cohort studies of DES-exposed women that had begun in the mid-1970s, so that the pooled subjects could be followed periodically with self-report questionnaires. Their Combined Cohort Study of DES Exposure involved 4,001 DES-exposed women and 1,683 nonexposed control subjects from the original cohorts, who were born between the late 1940s and the early 1960s and whose average age at last follow-up was 48 years.

Twelve adverse health outcomes that were significantly associated with DES in previous studies were assessed in the combined cohort, and all 12 were found to be significantly associated with DES in this combined analysis.

The hazard ratios (HRs) associated with DES exposure, compared with nonexposure, ranged from a low of 1.42 for preeclampsia to a high of 8.12 for neonatal death (usually related to preterm delivery). In ascending order, the HRs were 1.64 for spontaneous abortion; 1.82 for breast cancer diagnosed at age 40 or older; 2.28 for cervical intraepithelial neoplasia of grade 2 or higher; 2.35 for early menopause; 2.37 for infertility; 2.45 for stillbirth; 3.72 for ectopic pregnancy; 3.77 for loss of second-trimester pregnancy; and 4.68 for preterm delivery, the investigators wrote (N. Engl. J. Med. 2011;365:1304-14).

DES-exposed women who had clinical evidence of vaginal epithelial changes at a young age – a marker of high DES dose and exposure early in gestation – were found to have significantly higher risks for adverse outcomes than did exposed women who showed no vaginal epithelial changes. This finding provides additional support for the argument that DES exposure caused, and was not just linked to, the adverse outcomes, they said.

The researchers also calculated the excess risk of adverse outcomes that could be attributed directly to DES exposure. This excess risk was 1.7% for breast cancer, 3.4% for early menopause, 3.5% for CIN, 6.3% for stillbirth, 7.2% for neonatal death, 11.7% for both spontaneous abortion and ectopic pregnancy, 12.7% for preeclampsia, 14.7% for loss of second-trimester pregnancy, 17.8% for infertility, and 35.4% for preterm delivery.

The Combined Cohort Study of DES Exposure was supported by the National Cancer Institute. Dr. Robboy reports receiving consulting fees from UCB, Belgium. Dr. Karlan reports holding stock in and receiving board membership fees from IRIS International. Dr. Hatch receives royalties as a reviewer of the DES card on the UpToDate medical information site.

In-utero exposure to diethylstilbestrol was associated with a high lifetime risk of a broad spectrum of adverse outcomes in a follow-up study of patients now in their 40s, 50s, and 60s.

Most of these risks were increased by a factor of more than two, compared with the risks in women of the same age who were not exposed to diethylstilbestrol (DES), said Dr. Robert N. Hoover of the National Cancer Institute, Bethesda, Md., and his associates. “Although DES has not been prescribed for pregnant women in the United States for 40 years, adverse outcomes continue to occur in women exposed in utero, and continued monitoring … for established and unexpected adverse outcomes seems prudent,” they noted.

In the early 1990s, Dr. Hoover and his colleagues combined three cohort studies of DES-exposed women that had begun in the mid-1970s, so that the pooled subjects could be followed periodically with self-report questionnaires. Their Combined Cohort Study of DES Exposure involved 4,001 DES-exposed women and 1,683 nonexposed control subjects from the original cohorts, who were born between the late 1940s and the early 1960s and whose average age at last follow-up was 48 years.

Twelve adverse health outcomes that were significantly associated with DES in previous studies were assessed in the combined cohort, and all 12 were found to be significantly associated with DES in this combined analysis.

The hazard ratios (HRs) associated with DES exposure, compared with nonexposure, ranged from a low of 1.42 for preeclampsia to a high of 8.12 for neonatal death (usually related to preterm delivery). In ascending order, the HRs were 1.64 for spontaneous abortion; 1.82 for breast cancer diagnosed at age 40 or older; 2.28 for cervical intraepithelial neoplasia of grade 2 or higher; 2.35 for early menopause; 2.37 for infertility; 2.45 for stillbirth; 3.72 for ectopic pregnancy; 3.77 for loss of second-trimester pregnancy; and 4.68 for preterm delivery, the investigators wrote (N. Engl. J. Med. 2011;365:1304-14).

DES-exposed women who had clinical evidence of vaginal epithelial changes at a young age – a marker of high DES dose and exposure early in gestation – were found to have significantly higher risks for adverse outcomes than did exposed women who showed no vaginal epithelial changes. This finding provides additional support for the argument that DES exposure caused, and was not just linked to, the adverse outcomes, they said.

The researchers also calculated the excess risk of adverse outcomes that could be attributed directly to DES exposure. This excess risk was 1.7% for breast cancer, 3.4% for early menopause, 3.5% for CIN, 6.3% for stillbirth, 7.2% for neonatal death, 11.7% for both spontaneous abortion and ectopic pregnancy, 12.7% for preeclampsia, 14.7% for loss of second-trimester pregnancy, 17.8% for infertility, and 35.4% for preterm delivery.

The Combined Cohort Study of DES Exposure was supported by the National Cancer Institute. Dr. Robboy reports receiving consulting fees from UCB, Belgium. Dr. Karlan reports holding stock in and receiving board membership fees from IRIS International. Dr. Hatch receives royalties as a reviewer of the DES card on the UpToDate medical information site.

Women who don’t carry their family’s BRCA1 or BRCA2 mutation showed no increase in breast cancer risk in a study of 3,047 population-based families reported online Oct. 31 in the Journal of Clinical Oncology.

"These results support the standard clinical practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA mutation and, in the absence of other strong risk factors, should follow general population guidelines for breast cancer screening," said Dr. Allison W. Kurian of Stanford (Calif.) University and her associates.

Some recent studies have suggested that noncarriers of a family-specific mutation may have a two- to fivefold increase in risk of developing breast cancer, compared with the general population. While lower than the 5- to 20-fold increase in risk for carriers of the mutation, this rate would still be high enough to warrant breast cancer surveillance. Other studies have found no increase in risk among noncarriers.

To clarify the issue, Dr. Kurian and her colleagues assessed breast cancer risk using population-based cancer registries in the United States, Australia, and Canada. They identified 3,047 families in which one woman (the proband) was diagnosed as having breast cancer at a relatively young age, in most cases during 1996-2000, and she and her female first-degree relatives underwent genetic testing for BRCA1 and BRCA2 mutations.

Women in all three countries showed a similar prevalence of the mutations, similar rates of breast and ovarian cancer, and similar ages of onset for the malignancies. Overall, 160 families had BRCA1 mutations and 132 had BRCA2 mutations, the investigators reported (J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200.JCO.2010.34.4440]).

Among noncarriers of family-specific mutations, the risk of developing breast cancer was not significantly higher than the risk among women in families without any BRCA1 or BRCA2 mutations. This relative risk was 0.39.

It is possible that previous studies reporting an increased risk in noncarriers have overestimated this risk, because they compared study subjects with women in the general population rather than women whose relatives have breast cancer. The latter group undergoes more frequent screening and consequently has more frequent diagnoses of breast cancer than women in the general population, Dr. Kurian and her associates noted.

Their study, in which 292 families with BRCA1 or BRCA2 mutations were compared with 2,755 families without such mutations from the same populations, "represents the largest analysis to date of breast cancer risk to noncarriers of family-specific mutations," they added.

The study was supported by the National Cancer Institute, the National Institutes of Health, Cancer Care Ontario, Cancer Prevention Institute of California, and the University of Melbourne. No financial conflicts of interest were reported.

Women who don’t carry their family’s BRCA1 or BRCA2 mutation showed no increase in breast cancer risk in a study of 3,047 population-based families reported online Oct. 31 in the Journal of Clinical Oncology.

"These results support the standard clinical practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA mutation and, in the absence of other strong risk factors, should follow general population guidelines for breast cancer screening," said Dr. Allison W. Kurian of Stanford (Calif.) University and her associates.

Some recent studies have suggested that noncarriers of a family-specific mutation may have a two- to fivefold increase in risk of developing breast cancer, compared with the general population. While lower than the 5- to 20-fold increase in risk for carriers of the mutation, this rate would still be high enough to warrant breast cancer surveillance. Other studies have found no increase in risk among noncarriers.

To clarify the issue, Dr. Kurian and her colleagues assessed breast cancer risk using population-based cancer registries in the United States, Australia, and Canada. They identified 3,047 families in which one woman (the proband) was diagnosed as having breast cancer at a relatively young age, in most cases during 1996-2000, and she and her female first-degree relatives underwent genetic testing for BRCA1 and BRCA2 mutations.

Women in all three countries showed a similar prevalence of the mutations, similar rates of breast and ovarian cancer, and similar ages of onset for the malignancies. Overall, 160 families had BRCA1 mutations and 132 had BRCA2 mutations, the investigators reported (J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200.JCO.2010.34.4440]).

Among noncarriers of family-specific mutations, the risk of developing breast cancer was not significantly higher than the risk among women in families without any BRCA1 or BRCA2 mutations. This relative risk was 0.39.

It is possible that previous studies reporting an increased risk in noncarriers have overestimated this risk, because they compared study subjects with women in the general population rather than women whose relatives have breast cancer. The latter group undergoes more frequent screening and consequently has more frequent diagnoses of breast cancer than women in the general population, Dr. Kurian and her associates noted.

Their study, in which 292 families with BRCA1 or BRCA2 mutations were compared with 2,755 families without such mutations from the same populations, "represents the largest analysis to date of breast cancer risk to noncarriers of family-specific mutations," they added.

The study was supported by the National Cancer Institute, the National Institutes of Health, Cancer Care Ontario, Cancer Prevention Institute of California, and the University of Melbourne. No financial conflicts of interest were reported.

Women who don’t carry their family’s BRCA1 or BRCA2 mutation showed no increase in breast cancer risk in a study of 3,047 population-based families reported online Oct. 31 in the Journal of Clinical Oncology.

"These results support the standard clinical practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA mutation and, in the absence of other strong risk factors, should follow general population guidelines for breast cancer screening," said Dr. Allison W. Kurian of Stanford (Calif.) University and her associates.

Some recent studies have suggested that noncarriers of a family-specific mutation may have a two- to fivefold increase in risk of developing breast cancer, compared with the general population. While lower than the 5- to 20-fold increase in risk for carriers of the mutation, this rate would still be high enough to warrant breast cancer surveillance. Other studies have found no increase in risk among noncarriers.

To clarify the issue, Dr. Kurian and her colleagues assessed breast cancer risk using population-based cancer registries in the United States, Australia, and Canada. They identified 3,047 families in which one woman (the proband) was diagnosed as having breast cancer at a relatively young age, in most cases during 1996-2000, and she and her female first-degree relatives underwent genetic testing for BRCA1 and BRCA2 mutations.

Women in all three countries showed a similar prevalence of the mutations, similar rates of breast and ovarian cancer, and similar ages of onset for the malignancies. Overall, 160 families had BRCA1 mutations and 132 had BRCA2 mutations, the investigators reported (J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200.JCO.2010.34.4440]).

Among noncarriers of family-specific mutations, the risk of developing breast cancer was not significantly higher than the risk among women in families without any BRCA1 or BRCA2 mutations. This relative risk was 0.39.

It is possible that previous studies reporting an increased risk in noncarriers have overestimated this risk, because they compared study subjects with women in the general population rather than women whose relatives have breast cancer. The latter group undergoes more frequent screening and consequently has more frequent diagnoses of breast cancer than women in the general population, Dr. Kurian and her associates noted.

Their study, in which 292 families with BRCA1 or BRCA2 mutations were compared with 2,755 families without such mutations from the same populations, "represents the largest analysis to date of breast cancer risk to noncarriers of family-specific mutations," they added.

The study was supported by the National Cancer Institute, the National Institutes of Health, Cancer Care Ontario, Cancer Prevention Institute of California, and the University of Melbourne. No financial conflicts of interest were reported.

Briakinumab was more effective than methotrexate at reducing the signs and symptoms of moderate to severe plaque psoriasis in a 52-week, phase-III study reported in the Oct. 27 issue of the New England Journal of Medicine.

However, serious adverse events, adverse events leading to withdrawal from the study, serious infections, and cancers occurred more often with briakinumab, a monoclonal antibody that targets the "p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions," according to Dr. Kristian Reich, medical director of the Dermatologikum Hamburg, and his associates. However, "Too few patients were enrolled in the study to draw conclusions regarding these adverse events."

In the study, conducted at 43 sites in Europe and Canada and funded by Abbott Laboratories, 317 patients with stable plaque psoriasis were randomly assigned to receive subcutaneous briakinumab (154 subjects) or oral methotrexate plus oral folate (163 subjects) in a double-blind fashion. Efficacy was assessed at week 24 and week 52 (N. Engl. J. Med. 2011;365:1586-96).

Significantly more patients in the briakinumab group showed at least a 75% improvement in their score on the psoriasis area and severity index (PASI) at both week 24 (81.8%) and week 52 (66.2%), compared with patients on methotrexate (39.9% at week 24 and 23.9% at week 52). The median time to such improvement was 56 days with briakinumab, compared with 140 days with methotrexate.

In addition, "the percentage of patients who had at least 75% improvement in the PASI score was significantly greater in the briakinumab group than in the methotrexate group by week 4 and at all time points through week 52," Dr. Reich and his colleagues reported.

The difference between the two groups became significant at week 2, and the difference in the proportion of patients showing 90%-100% improvement became significant at week 8.

Also, significantly more patients who received briakinumab met the efficacy end point of a score of 0-1 on a 5-point measure of the physician’s global assessment at both week 24 (80.5% vs. 34.4%) and week 52 (63.0% vs. 20.2%). Significantly more patients receiving briakinumab (46.1%) than methotrexate (9.2%) had a score of 0, indicating complete clearing at week 24, with similar results at week 52 (45.5% vs. 9.8%, respectively).

The median time to achieving a score of 0-1 on the physician’s global assessment was 69 days with briakinumab, compared with 171 days with methotrexate. And significantly more patients in the briakinumab group had a score of 0-1 at every time point from week 4 through week 52.

On the Dermatology Quality of Life Index, which measures the impact of skin disease on quality of life, more patients taking briakinumab (70.8%) than methotrexate (34.4%) had a score of 0-1, indicating minimal impact at week 24, as well as at week 52 (61.7% vs 17.8%, respectively). And significantly more patients taking briakinumab had a clinically meaningful reduction in Dermatology Quality of Life Index score at all time points.

In all, 12 patients in the briakinumab group (7.8%) and 10 in the methotrexate group (6.1%) withdrew from the study because of adverse events. The incidence of serious infections was 4.1 per 100 patient-years with briakinumab and 2.7 per 100 patient-years with methotrexate.

The four serious infections with briakinumab included one case of legionella with candidemia and septic shock, one case of osteomyelitis, one case of herpes zoster, and one case of tonsillitis. In the methotrexate group, there were two cases of diverticulitis and one case of hepatitis.

Three patients in the briakinumab group were diagnosed with cancer. And one death was reported: a patient receiving methotrexate died from an esophageal rupture.

This study was supported by Abbott, maker of briakinumab. Dr. Reich and his associates reported ties to Amgen, Astellas Celgene, Centocor, Biogen-Idec, Galderma, Janssen-Cilag, Graceway, Johnson & Johnson, LEO-Pharma, Meda-Pharma, Merck, Novartis, Ortho Biotech, Pfizer, Schering-Plough, UCB, and Wyeth.

Briakinumab was more effective than methotrexate at reducing the signs and symptoms of moderate to severe plaque psoriasis in a 52-week, phase-III study reported in the Oct. 27 issue of the New England Journal of Medicine.

However, serious adverse events, adverse events leading to withdrawal from the study, serious infections, and cancers occurred more often with briakinumab, a monoclonal antibody that targets the "p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions," according to Dr. Kristian Reich, medical director of the Dermatologikum Hamburg, and his associates. However, "Too few patients were enrolled in the study to draw conclusions regarding these adverse events."

In the study, conducted at 43 sites in Europe and Canada and funded by Abbott Laboratories, 317 patients with stable plaque psoriasis were randomly assigned to receive subcutaneous briakinumab (154 subjects) or oral methotrexate plus oral folate (163 subjects) in a double-blind fashion. Efficacy was assessed at week 24 and week 52 (N. Engl. J. Med. 2011;365:1586-96).

Significantly more patients in the briakinumab group showed at least a 75% improvement in their score on the psoriasis area and severity index (PASI) at both week 24 (81.8%) and week 52 (66.2%), compared with patients on methotrexate (39.9% at week 24 and 23.9% at week 52). The median time to such improvement was 56 days with briakinumab, compared with 140 days with methotrexate.

In addition, "the percentage of patients who had at least 75% improvement in the PASI score was significantly greater in the briakinumab group than in the methotrexate group by week 4 and at all time points through week 52," Dr. Reich and his colleagues reported.

The difference between the two groups became significant at week 2, and the difference in the proportion of patients showing 90%-100% improvement became significant at week 8.

Also, significantly more patients who received briakinumab met the efficacy end point of a score of 0-1 on a 5-point measure of the physician’s global assessment at both week 24 (80.5% vs. 34.4%) and week 52 (63.0% vs. 20.2%). Significantly more patients receiving briakinumab (46.1%) than methotrexate (9.2%) had a score of 0, indicating complete clearing at week 24, with similar results at week 52 (45.5% vs. 9.8%, respectively).

The median time to achieving a score of 0-1 on the physician’s global assessment was 69 days with briakinumab, compared with 171 days with methotrexate. And significantly more patients in the briakinumab group had a score of 0-1 at every time point from week 4 through week 52.

On the Dermatology Quality of Life Index, which measures the impact of skin disease on quality of life, more patients taking briakinumab (70.8%) than methotrexate (34.4%) had a score of 0-1, indicating minimal impact at week 24, as well as at week 52 (61.7% vs 17.8%, respectively). And significantly more patients taking briakinumab had a clinically meaningful reduction in Dermatology Quality of Life Index score at all time points.

In all, 12 patients in the briakinumab group (7.8%) and 10 in the methotrexate group (6.1%) withdrew from the study because of adverse events. The incidence of serious infections was 4.1 per 100 patient-years with briakinumab and 2.7 per 100 patient-years with methotrexate.

The four serious infections with briakinumab included one case of legionella with candidemia and septic shock, one case of osteomyelitis, one case of herpes zoster, and one case of tonsillitis. In the methotrexate group, there were two cases of diverticulitis and one case of hepatitis.

Three patients in the briakinumab group were diagnosed with cancer. And one death was reported: a patient receiving methotrexate died from an esophageal rupture.

This study was supported by Abbott, maker of briakinumab. Dr. Reich and his associates reported ties to Amgen, Astellas Celgene, Centocor, Biogen-Idec, Galderma, Janssen-Cilag, Graceway, Johnson & Johnson, LEO-Pharma, Meda-Pharma, Merck, Novartis, Ortho Biotech, Pfizer, Schering-Plough, UCB, and Wyeth.

Briakinumab was more effective than methotrexate at reducing the signs and symptoms of moderate to severe plaque psoriasis in a 52-week, phase-III study reported in the Oct. 27 issue of the New England Journal of Medicine.

However, serious adverse events, adverse events leading to withdrawal from the study, serious infections, and cancers occurred more often with briakinumab, a monoclonal antibody that targets the "p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions," according to Dr. Kristian Reich, medical director of the Dermatologikum Hamburg, and his associates. However, "Too few patients were enrolled in the study to draw conclusions regarding these adverse events."

In the study, conducted at 43 sites in Europe and Canada and funded by Abbott Laboratories, 317 patients with stable plaque psoriasis were randomly assigned to receive subcutaneous briakinumab (154 subjects) or oral methotrexate plus oral folate (163 subjects) in a double-blind fashion. Efficacy was assessed at week 24 and week 52 (N. Engl. J. Med. 2011;365:1586-96).

Significantly more patients in the briakinumab group showed at least a 75% improvement in their score on the psoriasis area and severity index (PASI) at both week 24 (81.8%) and week 52 (66.2%), compared with patients on methotrexate (39.9% at week 24 and 23.9% at week 52). The median time to such improvement was 56 days with briakinumab, compared with 140 days with methotrexate.

In addition, "the percentage of patients who had at least 75% improvement in the PASI score was significantly greater in the briakinumab group than in the methotrexate group by week 4 and at all time points through week 52," Dr. Reich and his colleagues reported.

The difference between the two groups became significant at week 2, and the difference in the proportion of patients showing 90%-100% improvement became significant at week 8.

Also, significantly more patients who received briakinumab met the efficacy end point of a score of 0-1 on a 5-point measure of the physician’s global assessment at both week 24 (80.5% vs. 34.4%) and week 52 (63.0% vs. 20.2%). Significantly more patients receiving briakinumab (46.1%) than methotrexate (9.2%) had a score of 0, indicating complete clearing at week 24, with similar results at week 52 (45.5% vs. 9.8%, respectively).

The median time to achieving a score of 0-1 on the physician’s global assessment was 69 days with briakinumab, compared with 171 days with methotrexate. And significantly more patients in the briakinumab group had a score of 0-1 at every time point from week 4 through week 52.

On the Dermatology Quality of Life Index, which measures the impact of skin disease on quality of life, more patients taking briakinumab (70.8%) than methotrexate (34.4%) had a score of 0-1, indicating minimal impact at week 24, as well as at week 52 (61.7% vs 17.8%, respectively). And significantly more patients taking briakinumab had a clinically meaningful reduction in Dermatology Quality of Life Index score at all time points.

In all, 12 patients in the briakinumab group (7.8%) and 10 in the methotrexate group (6.1%) withdrew from the study because of adverse events. The incidence of serious infections was 4.1 per 100 patient-years with briakinumab and 2.7 per 100 patient-years with methotrexate.

The four serious infections with briakinumab included one case of legionella with candidemia and septic shock, one case of osteomyelitis, one case of herpes zoster, and one case of tonsillitis. In the methotrexate group, there were two cases of diverticulitis and one case of hepatitis.

Three patients in the briakinumab group were diagnosed with cancer. And one death was reported: a patient receiving methotrexate died from an esophageal rupture.

This study was supported by Abbott, maker of briakinumab. Dr. Reich and his associates reported ties to Amgen, Astellas Celgene, Centocor, Biogen-Idec, Galderma, Janssen-Cilag, Graceway, Johnson & Johnson, LEO-Pharma, Meda-Pharma, Merck, Novartis, Ortho Biotech, Pfizer, Schering-Plough, UCB, and Wyeth.

The quadrivalent HPV vaccine reduced the rate of persistent anal infection with HPV types 6, 11, 16, and 18, as well as the anal intraepithelial neoplasia associated with these viral types, in an industry-sponsored study of homosexual men reported in the Oct. 27 issue of the New England Journal of Medicine.

It is likely that the vaccine will also prevent anal cancer, but longer follow-up is needed to make that determination, said Dr. Joel M. Palefsky of the University of California, San Francisco, and his associates.

"Although our study only included men who have sex with men, our data suggest potential benefits of vaccination for women and heterosexual men, beyond the already demonstrated protection against cervical and vulvovaginal disease and external genital condyloma. ... We would expect the qHPV vaccine to protect against anal intraepithelial neoplasia [including anal condyloma] in the female and heterosexual male populations to a degree similar to that among men who have sex with men," they noted.

The incidence of anal cancer has been increasing by approximately 2% per year in both men and women in the general population. Anal condyloma is more common – one of the most common sexually transmitted diseases (STDs) in homosexual men. This condition can cause substantial psychological distress, and may be painful and expensive to treat. So the HPV vaccine’s ability to reduce anal condyloma is "a substantial added benefit," the researchers said.

Dr. Palefsky and his colleagues assessed the efficacy of the quadrivalent HPV vaccine at preventing anal lesions in 598 healthy homosexual men aged 16-26 years residing in the United States, Australia, Brazil, Canada, Croatia, Germany, and Spain. Half the subjects were randomly assigned to receive serial injections of active vaccine, and half received placebo injections over the course of 1 month.

The two groups were well-matched for age, race, ethnicity, geographic region, smoking status, circumcision status, and sexual history. Vaccine efficacy was determined at 7 months after vaccination, and the study subjects were followed for a mean of 2.2 years after that.

As expected, no cases of anal cancer developed in these young study subjects followed for a relatively short time.

The vaccine had an overall efficacy of 77.5% in preventing anal intraepithelial neoplasia or anal cancer related to HPV-6, 11, 16, or 18 in the per-protocol study population. (This included only subjects whose swab and biopsy specimens were negative for vaccine-type DNA through 7 months.) Such lesions developed in 5 men who received active vaccine and 24 who received placebo.

The vaccine was 73% efficacious against anal intraepithelial neoplasia of grade 1, including condyloma, and 74.9% efficacious against anal intraepithelial neoplasia of grade 2 or 3 in the per-protocol population.

In the intention-to-treat population, vaccine efficacy against anal intraepithelial neoplasia related to any of the four HPV types was 50.3%. "Significant reductions in both anal intraepithelial neoplasia of grade 1 (49.6%) and ... grade 2 or 3 (54.2%) were seen in the intention-to-treat population," the investigators said (N. Engl. J. Med. 2011;365:1576-85).

In addition, the vaccine reduced persistent HPV infection with an efficacy of 94.9% in the per-protocol population and 59.4% in the intention-to-treat population. Persistent infection was defined as detection of the same HPV type at two or more consecutive visits that were at least 4 months apart.

Dr. Palefsky and his associates noted that "the proportion of patients who reported serious adverse events or who discontinued the study owing to an adverse event was relatively low and was similar in the two groups." There were no vaccine-related serious adverse events and no deaths in either group.

It is important to note that these study subjects had somewhat limited sexual experience, with a maximum of five lifetime sexual partners. Thus, the findings may not be generalizable to other men who have sex with men, who tend to have more sexual partners, the researchers added.

This study was funded by Merck, maker of the Gardasil and Silgard HPV vaccines, with additional support from the National Institutes of Health. Dr. Palefsky reported ties to Merck, Pharmajet, and Aura Biosciences; his associates reported numerous industry ties.

The quadrivalent HPV vaccine reduced the rate of persistent anal infection with HPV types 6, 11, 16, and 18, as well as the anal intraepithelial neoplasia associated with these viral types, in an industry-sponsored study of homosexual men reported in the Oct. 27 issue of the New England Journal of Medicine.

It is likely that the vaccine will also prevent anal cancer, but longer follow-up is needed to make that determination, said Dr. Joel M. Palefsky of the University of California, San Francisco, and his associates.

"Although our study only included men who have sex with men, our data suggest potential benefits of vaccination for women and heterosexual men, beyond the already demonstrated protection against cervical and vulvovaginal disease and external genital condyloma. ... We would expect the qHPV vaccine to protect against anal intraepithelial neoplasia [including anal condyloma] in the female and heterosexual male populations to a degree similar to that among men who have sex with men," they noted.

The incidence of anal cancer has been increasing by approximately 2% per year in both men and women in the general population. Anal condyloma is more common – one of the most common sexually transmitted diseases (STDs) in homosexual men. This condition can cause substantial psychological distress, and may be painful and expensive to treat. So the HPV vaccine’s ability to reduce anal condyloma is "a substantial added benefit," the researchers said.

Dr. Palefsky and his colleagues assessed the efficacy of the quadrivalent HPV vaccine at preventing anal lesions in 598 healthy homosexual men aged 16-26 years residing in the United States, Australia, Brazil, Canada, Croatia, Germany, and Spain. Half the subjects were randomly assigned to receive serial injections of active vaccine, and half received placebo injections over the course of 1 month.

The two groups were well-matched for age, race, ethnicity, geographic region, smoking status, circumcision status, and sexual history. Vaccine efficacy was determined at 7 months after vaccination, and the study subjects were followed for a mean of 2.2 years after that.

As expected, no cases of anal cancer developed in these young study subjects followed for a relatively short time.

The vaccine had an overall efficacy of 77.5% in preventing anal intraepithelial neoplasia or anal cancer related to HPV-6, 11, 16, or 18 in the per-protocol study population. (This included only subjects whose swab and biopsy specimens were negative for vaccine-type DNA through 7 months.) Such lesions developed in 5 men who received active vaccine and 24 who received placebo.

The vaccine was 73% efficacious against anal intraepithelial neoplasia of grade 1, including condyloma, and 74.9% efficacious against anal intraepithelial neoplasia of grade 2 or 3 in the per-protocol population.

In the intention-to-treat population, vaccine efficacy against anal intraepithelial neoplasia related to any of the four HPV types was 50.3%. "Significant reductions in both anal intraepithelial neoplasia of grade 1 (49.6%) and ... grade 2 or 3 (54.2%) were seen in the intention-to-treat population," the investigators said (N. Engl. J. Med. 2011;365:1576-85).

In addition, the vaccine reduced persistent HPV infection with an efficacy of 94.9% in the per-protocol population and 59.4% in the intention-to-treat population. Persistent infection was defined as detection of the same HPV type at two or more consecutive visits that were at least 4 months apart.

Dr. Palefsky and his associates noted that "the proportion of patients who reported serious adverse events or who discontinued the study owing to an adverse event was relatively low and was similar in the two groups." There were no vaccine-related serious adverse events and no deaths in either group.

It is important to note that these study subjects had somewhat limited sexual experience, with a maximum of five lifetime sexual partners. Thus, the findings may not be generalizable to other men who have sex with men, who tend to have more sexual partners, the researchers added.

This study was funded by Merck, maker of the Gardasil and Silgard HPV vaccines, with additional support from the National Institutes of Health. Dr. Palefsky reported ties to Merck, Pharmajet, and Aura Biosciences; his associates reported numerous industry ties.

The quadrivalent HPV vaccine reduced the rate of persistent anal infection with HPV types 6, 11, 16, and 18, as well as the anal intraepithelial neoplasia associated with these viral types, in an industry-sponsored study of homosexual men reported in the Oct. 27 issue of the New England Journal of Medicine.

It is likely that the vaccine will also prevent anal cancer, but longer follow-up is needed to make that determination, said Dr. Joel M. Palefsky of the University of California, San Francisco, and his associates.

"Although our study only included men who have sex with men, our data suggest potential benefits of vaccination for women and heterosexual men, beyond the already demonstrated protection against cervical and vulvovaginal disease and external genital condyloma. ... We would expect the qHPV vaccine to protect against anal intraepithelial neoplasia [including anal condyloma] in the female and heterosexual male populations to a degree similar to that among men who have sex with men," they noted.

The incidence of anal cancer has been increasing by approximately 2% per year in both men and women in the general population. Anal condyloma is more common – one of the most common sexually transmitted diseases (STDs) in homosexual men. This condition can cause substantial psychological distress, and may be painful and expensive to treat. So the HPV vaccine’s ability to reduce anal condyloma is "a substantial added benefit," the researchers said.

Dr. Palefsky and his colleagues assessed the efficacy of the quadrivalent HPV vaccine at preventing anal lesions in 598 healthy homosexual men aged 16-26 years residing in the United States, Australia, Brazil, Canada, Croatia, Germany, and Spain. Half the subjects were randomly assigned to receive serial injections of active vaccine, and half received placebo injections over the course of 1 month.

The two groups were well-matched for age, race, ethnicity, geographic region, smoking status, circumcision status, and sexual history. Vaccine efficacy was determined at 7 months after vaccination, and the study subjects were followed for a mean of 2.2 years after that.

As expected, no cases of anal cancer developed in these young study subjects followed for a relatively short time.

The vaccine had an overall efficacy of 77.5% in preventing anal intraepithelial neoplasia or anal cancer related to HPV-6, 11, 16, or 18 in the per-protocol study population. (This included only subjects whose swab and biopsy specimens were negative for vaccine-type DNA through 7 months.) Such lesions developed in 5 men who received active vaccine and 24 who received placebo.

The vaccine was 73% efficacious against anal intraepithelial neoplasia of grade 1, including condyloma, and 74.9% efficacious against anal intraepithelial neoplasia of grade 2 or 3 in the per-protocol population.

In the intention-to-treat population, vaccine efficacy against anal intraepithelial neoplasia related to any of the four HPV types was 50.3%. "Significant reductions in both anal intraepithelial neoplasia of grade 1 (49.6%) and ... grade 2 or 3 (54.2%) were seen in the intention-to-treat population," the investigators said (N. Engl. J. Med. 2011;365:1576-85).

In addition, the vaccine reduced persistent HPV infection with an efficacy of 94.9% in the per-protocol population and 59.4% in the intention-to-treat population. Persistent infection was defined as detection of the same HPV type at two or more consecutive visits that were at least 4 months apart.

Dr. Palefsky and his associates noted that "the proportion of patients who reported serious adverse events or who discontinued the study owing to an adverse event was relatively low and was similar in the two groups." There were no vaccine-related serious adverse events and no deaths in either group.

It is important to note that these study subjects had somewhat limited sexual experience, with a maximum of five lifetime sexual partners. Thus, the findings may not be generalizable to other men who have sex with men, who tend to have more sexual partners, the researchers added.

This study was funded by Merck, maker of the Gardasil and Silgard HPV vaccines, with additional support from the National Institutes of Health. Dr. Palefsky reported ties to Merck, Pharmajet, and Aura Biosciences; his associates reported numerous industry ties.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

The probability that a breast cancer patient’s life was saved by mammography screening is always less than 25%, according to various "plausible estimates" of the risk of developing and dying from breast cancer published online Oct. 24 in the Archives of Internal Medicine.

In fact, given that the most recent data "confirm that the current benefit of screening mammography is disappointingly small," the probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%," said Dr. H. Gilbert Welch and Ms. Brittney A. Frankel of the Dartmouth Institute for Health Policy and Clinical Practice, Hanover, N.H.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

More people are likely to personally know a cancer survivor than ever before, as the proportion of survivors in the general U.S. population has more than doubled in recent years and now stands at 4%. "Breast cancer survivors are particularly common: they now represent approximately 2.5 million, or one-fifth of the current survivor population."

And "survivor stories" feed the public’s presumption that every survivor whose cancer was detected by mammography has had her life saved by that screening. Most people don’t realize that in many cases, the cancer would have been equally treatable if it hadn’t been detected until it presented clinically. And in many other cases, the malignancy was "overdiagnosed" – it would never have caused symptoms or death if it had been left undetected and untreated.

"It is important to acknowledge that these alternatives exist," they wrote.

They calculated the probabilities that a screening mammography saved a patient’s life using the National Cancer Institute’s DevCan 6.5.0, a tool that helps compute the risks of developing and of dying from cancer at specific ages, based on detailed national epidemiologic data. "The risk of having screen-detected cancer was estimated simply as the product of the risk of developing breast cancer and the proportion of breast cancers found by mammography," they said.

"The absolute risk reduction in mortality due to mammography, or mortality benefit, was calculated as the difference between the estimated 20-year risk of death without mammography and the 20-year risk of death observed currently. The probability that a woman with screen-detected breast cancer has avoided breast cancer death because of screening was the ratio of the mortality benefit and the probability of having screen-detected breast cancer," they noted.

Their results show the estimated relative risk reduction in breast cancer mortality at ages 40, 50, 60, and 70 years, under a variety of conditions.

For example, assuming that screening mammography reduces the risk of breast cancer death by 20% for a 50-year-old woman, the probability that such a 50-year-old woman with a mammography-detected breast cancer has avoided a death from breast cancer is 13%.

The probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%."

If one of the underlying assumptions is changed – for example, assuming that screening mammography reduces the risk of breast cancer by 25% rather than 20% – this probability rises to 17%. If one assumes that screening mammography instead reduces the risk of breast cancer by only 5%, this probability falls to 3%.

The researchers discovered that "the most dramatic" effect of screening mammography on survival occurs in the 70-year-old age group, "because the proportion of screen-detected cancers in this age group is relatively low (52%)." Nevertheless, even in this group the probability that screening mammography saves a woman from breast cancer death remained under 25%.

"All analyses yielded probability estimates below 25%," Dr. Welch and Ms. Frankel noted (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.476]).

The benefit of screening mammography has declined over time, in part because women present earlier when they find a breast lump on their own and in part because treatment of such cancers has improved. "Consequently, we believe that readers should focus on the values toward the low end (5%-10%) and recognize that the probability that a woman with screen-detected breast cancer has, in fact, avoided a breast cancer death because of screening mammography is now likely to be well below 10%," they added.

It is important to use this information "to put cancer survivor stories in their proper context," the investigators said.

No financial conflicts of interest were reported.

The probability that a breast cancer patient’s life was saved by mammography screening is always less than 25%, according to various "plausible estimates" of the risk of developing and dying from breast cancer published online Oct. 24 in the Archives of Internal Medicine.

In fact, given that the most recent data "confirm that the current benefit of screening mammography is disappointingly small," the probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%," said Dr. H. Gilbert Welch and Ms. Brittney A. Frankel of the Dartmouth Institute for Health Policy and Clinical Practice, Hanover, N.H.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

More people are likely to personally know a cancer survivor than ever before, as the proportion of survivors in the general U.S. population has more than doubled in recent years and now stands at 4%. "Breast cancer survivors are particularly common: they now represent approximately 2.5 million, or one-fifth of the current survivor population."

And "survivor stories" feed the public’s presumption that every survivor whose cancer was detected by mammography has had her life saved by that screening. Most people don’t realize that in many cases, the cancer would have been equally treatable if it hadn’t been detected until it presented clinically. And in many other cases, the malignancy was "overdiagnosed" – it would never have caused symptoms or death if it had been left undetected and untreated.

"It is important to acknowledge that these alternatives exist," they wrote.

They calculated the probabilities that a screening mammography saved a patient’s life using the National Cancer Institute’s DevCan 6.5.0, a tool that helps compute the risks of developing and of dying from cancer at specific ages, based on detailed national epidemiologic data. "The risk of having screen-detected cancer was estimated simply as the product of the risk of developing breast cancer and the proportion of breast cancers found by mammography," they said.

"The absolute risk reduction in mortality due to mammography, or mortality benefit, was calculated as the difference between the estimated 20-year risk of death without mammography and the 20-year risk of death observed currently. The probability that a woman with screen-detected breast cancer has avoided breast cancer death because of screening was the ratio of the mortality benefit and the probability of having screen-detected breast cancer," they noted.

Their results show the estimated relative risk reduction in breast cancer mortality at ages 40, 50, 60, and 70 years, under a variety of conditions.

For example, assuming that screening mammography reduces the risk of breast cancer death by 20% for a 50-year-old woman, the probability that such a 50-year-old woman with a mammography-detected breast cancer has avoided a death from breast cancer is 13%.

The probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%."

If one of the underlying assumptions is changed – for example, assuming that screening mammography reduces the risk of breast cancer by 25% rather than 20% – this probability rises to 17%. If one assumes that screening mammography instead reduces the risk of breast cancer by only 5%, this probability falls to 3%.

The researchers discovered that "the most dramatic" effect of screening mammography on survival occurs in the 70-year-old age group, "because the proportion of screen-detected cancers in this age group is relatively low (52%)." Nevertheless, even in this group the probability that screening mammography saves a woman from breast cancer death remained under 25%.

"All analyses yielded probability estimates below 25%," Dr. Welch and Ms. Frankel noted (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.476]).

The benefit of screening mammography has declined over time, in part because women present earlier when they find a breast lump on their own and in part because treatment of such cancers has improved. "Consequently, we believe that readers should focus on the values toward the low end (5%-10%) and recognize that the probability that a woman with screen-detected breast cancer has, in fact, avoided a breast cancer death because of screening mammography is now likely to be well below 10%," they added.

It is important to use this information "to put cancer survivor stories in their proper context," the investigators said.

No financial conflicts of interest were reported.

The probability that a breast cancer patient’s life was saved by mammography screening is always less than 25%, according to various "plausible estimates" of the risk of developing and dying from breast cancer published online Oct. 24 in the Archives of Internal Medicine.

In fact, given that the most recent data "confirm that the current benefit of screening mammography is disappointingly small," the probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%," said Dr. H. Gilbert Welch and Ms. Brittney A. Frankel of the Dartmouth Institute for Health Policy and Clinical Practice, Hanover, N.H.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

More people are likely to personally know a cancer survivor than ever before, as the proportion of survivors in the general U.S. population has more than doubled in recent years and now stands at 4%. "Breast cancer survivors are particularly common: they now represent approximately 2.5 million, or one-fifth of the current survivor population."

And "survivor stories" feed the public’s presumption that every survivor whose cancer was detected by mammography has had her life saved by that screening. Most people don’t realize that in many cases, the cancer would have been equally treatable if it hadn’t been detected until it presented clinically. And in many other cases, the malignancy was "overdiagnosed" – it would never have caused symptoms or death if it had been left undetected and untreated.

"It is important to acknowledge that these alternatives exist," they wrote.

They calculated the probabilities that a screening mammography saved a patient’s life using the National Cancer Institute’s DevCan 6.5.0, a tool that helps compute the risks of developing and of dying from cancer at specific ages, based on detailed national epidemiologic data. "The risk of having screen-detected cancer was estimated simply as the product of the risk of developing breast cancer and the proportion of breast cancers found by mammography," they said.

"The absolute risk reduction in mortality due to mammography, or mortality benefit, was calculated as the difference between the estimated 20-year risk of death without mammography and the 20-year risk of death observed currently. The probability that a woman with screen-detected breast cancer has avoided breast cancer death because of screening was the ratio of the mortality benefit and the probability of having screen-detected breast cancer," they noted.

Their results show the estimated relative risk reduction in breast cancer mortality at ages 40, 50, 60, and 70 years, under a variety of conditions.

For example, assuming that screening mammography reduces the risk of breast cancer death by 20% for a 50-year-old woman, the probability that such a 50-year-old woman with a mammography-detected breast cancer has avoided a death from breast cancer is 13%.

The probability that a typical woman whose breast cancer was detected by screening mammography owes her life to that procedure "is now likely to be well below 10%."

If one of the underlying assumptions is changed – for example, assuming that screening mammography reduces the risk of breast cancer by 25% rather than 20% – this probability rises to 17%. If one assumes that screening mammography instead reduces the risk of breast cancer by only 5%, this probability falls to 3%.

The researchers discovered that "the most dramatic" effect of screening mammography on survival occurs in the 70-year-old age group, "because the proportion of screen-detected cancers in this age group is relatively low (52%)." Nevertheless, even in this group the probability that screening mammography saves a woman from breast cancer death remained under 25%.

"All analyses yielded probability estimates below 25%," Dr. Welch and Ms. Frankel noted (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.476]).

The benefit of screening mammography has declined over time, in part because women present earlier when they find a breast lump on their own and in part because treatment of such cancers has improved. "Consequently, we believe that readers should focus on the values toward the low end (5%-10%) and recognize that the probability that a woman with screen-detected breast cancer has, in fact, avoided a breast cancer death because of screening mammography is now likely to be well below 10%," they added.

It is important to use this information "to put cancer survivor stories in their proper context," the investigators said.

No financial conflicts of interest were reported.

Stretching exercises in the form of either yoga or more conventional classes somewhat lessen chronic low-back pain that is moderately impairing, a study published online Oct. 24 in Archives of Internal Medicine has shown.

However, before referring patients to these classes, clinicians should ensure "sufficient back- and leg-focused stretching" is included and that instructors are willing to modify some of the traditional postures for people who have physical limitations, said Karen J. Sherman, Ph.D., of Group Health Research Institute, Seattle, and her associates.

The researchers compared the effectiveness of yoga classes, stretching classes, and usual self-care at relieving chronic low-back pain in a randomized controlled trial involving 228 adults residing in six cities in Western Washington. They hypothesized that yoga would prove superior to the other two interventions, because all eight clinical trials of yoga for this indication in the literature have shown it to be effective. However, the eight studies also had "considerable limitations," including small sample sizes, high attrition rates, and inconsistencies in the types of yoga provided, hours of class time, frequency of classes, and types of control situations.

In this trial, both yoga and stretching classes were held weekly for 75 minutes at Group Health facilities, for a total of 12 weeks. Patients were given CDs or DVDs to assist with home practice and were advised to practice 20 minutes on days when they weren’t attending class.

Patients were assessed via telephone interviews at baseline, 6 weeks, 12 weeks, and 26 weeks. The primary end point was self-rating at 26 weeks on the 23-item Roland-Morris Disability Questionnaire and on a scale of the bothersomeness of lower-back symptoms.

The yoga intervention (92 subjects) included breathing exercises, the use of 5-11 postures for 45-50 minutes (with adaptations allowed for patients’ limitations), and guided deep relaxation. Instructors had at least 500 hours of Viniyoga training and 5 years of teaching experience and were briefed by a study consultant who had expertise in low-back pain.

The stretching intervention (91 subjects) included aerobic activity, 10 strengthening exercises and 12 stretches held for 30 seconds each, and 52 minutes of 15 exercises that stretched all the major muscle groups but focused on the trunk and legs. Instructors were licensed physical therapists who had experience teaching classes and had completed a 2-hour training program for the study.

For the usual-care control condition (45 subjects), patients were given "The Back Pain Helpbook," which details the causes of back pain and makes recommendations regarding exercise, modifying lifestyle factors that contribute to back pain, and managing flares of back pain.

Back-related dysfunction declined over time in all three study groups, but the reduction was significantly greater with the yoga intervention and the stretching intervention. Contrary to their hypothesis, yoga classes did not prove superior to conventional stretching classes in this regard, Dr. Sherman and her colleagues said (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.524]).

Self-ratings of symptom bothersomeness did not differ significantly among the three groups.

Significantly more patients participating in both classes showed "substantial" (50% or more) clinical improvement from baseline: 52% of the yoga subjects and 56% of the stretching subjects reported this outcome, compared with only 23% of the control subjects.

Compared with the control group, both intervention groups were significantly more likely to describe their back pain as "better," "much better," or "completely gone" at all follow-up assessments, and were more likely to report they were "very satisfied" with their care.

The finding of such similar outcomes between the yoga group and the stretching group "suggests that yoga’s benefits were largely attributable to the physical benefits of stretching and strengthening the muscles and not to its mental components," the investigators said.

Thirteen patients (14%) in each intervention group reported mild or moderate adverse events that were possibly related to treatment, compared with only 1 control subject (0.02%).

Overall, the results of this study indicate that both yoga and stretching exercises are "reasonable treatment options for persons who are willing to engage in physical activities to relieve moderately impairing back pain," the researchers said.

This study was funded by the National Center for Complementary and Alternative Medicine. No relevant financial disclosures were reported by the authors.

Stretching exercises in the form of either yoga or more conventional classes somewhat lessen chronic low-back pain that is moderately impairing, a study published online Oct. 24 in Archives of Internal Medicine has shown.

However, before referring patients to these classes, clinicians should ensure "sufficient back- and leg-focused stretching" is included and that instructors are willing to modify some of the traditional postures for people who have physical limitations, said Karen J. Sherman, Ph.D., of Group Health Research Institute, Seattle, and her associates.

The researchers compared the effectiveness of yoga classes, stretching classes, and usual self-care at relieving chronic low-back pain in a randomized controlled trial involving 228 adults residing in six cities in Western Washington. They hypothesized that yoga would prove superior to the other two interventions, because all eight clinical trials of yoga for this indication in the literature have shown it to be effective. However, the eight studies also had "considerable limitations," including small sample sizes, high attrition rates, and inconsistencies in the types of yoga provided, hours of class time, frequency of classes, and types of control situations.

In this trial, both yoga and stretching classes were held weekly for 75 minutes at Group Health facilities, for a total of 12 weeks. Patients were given CDs or DVDs to assist with home practice and were advised to practice 20 minutes on days when they weren’t attending class.

Patients were assessed via telephone interviews at baseline, 6 weeks, 12 weeks, and 26 weeks. The primary end point was self-rating at 26 weeks on the 23-item Roland-Morris Disability Questionnaire and on a scale of the bothersomeness of lower-back symptoms.

The yoga intervention (92 subjects) included breathing exercises, the use of 5-11 postures for 45-50 minutes (with adaptations allowed for patients’ limitations), and guided deep relaxation. Instructors had at least 500 hours of Viniyoga training and 5 years of teaching experience and were briefed by a study consultant who had expertise in low-back pain.

The stretching intervention (91 subjects) included aerobic activity, 10 strengthening exercises and 12 stretches held for 30 seconds each, and 52 minutes of 15 exercises that stretched all the major muscle groups but focused on the trunk and legs. Instructors were licensed physical therapists who had experience teaching classes and had completed a 2-hour training program for the study.

For the usual-care control condition (45 subjects), patients were given "The Back Pain Helpbook," which details the causes of back pain and makes recommendations regarding exercise, modifying lifestyle factors that contribute to back pain, and managing flares of back pain.

Back-related dysfunction declined over time in all three study groups, but the reduction was significantly greater with the yoga intervention and the stretching intervention. Contrary to their hypothesis, yoga classes did not prove superior to conventional stretching classes in this regard, Dr. Sherman and her colleagues said (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.524]).

Self-ratings of symptom bothersomeness did not differ significantly among the three groups.

Significantly more patients participating in both classes showed "substantial" (50% or more) clinical improvement from baseline: 52% of the yoga subjects and 56% of the stretching subjects reported this outcome, compared with only 23% of the control subjects.

Compared with the control group, both intervention groups were significantly more likely to describe their back pain as "better," "much better," or "completely gone" at all follow-up assessments, and were more likely to report they were "very satisfied" with their care.

The finding of such similar outcomes between the yoga group and the stretching group "suggests that yoga’s benefits were largely attributable to the physical benefits of stretching and strengthening the muscles and not to its mental components," the investigators said.

Thirteen patients (14%) in each intervention group reported mild or moderate adverse events that were possibly related to treatment, compared with only 1 control subject (0.02%).

Overall, the results of this study indicate that both yoga and stretching exercises are "reasonable treatment options for persons who are willing to engage in physical activities to relieve moderately impairing back pain," the researchers said.

This study was funded by the National Center for Complementary and Alternative Medicine. No relevant financial disclosures were reported by the authors.

Stretching exercises in the form of either yoga or more conventional classes somewhat lessen chronic low-back pain that is moderately impairing, a study published online Oct. 24 in Archives of Internal Medicine has shown.

However, before referring patients to these classes, clinicians should ensure "sufficient back- and leg-focused stretching" is included and that instructors are willing to modify some of the traditional postures for people who have physical limitations, said Karen J. Sherman, Ph.D., of Group Health Research Institute, Seattle, and her associates.

The researchers compared the effectiveness of yoga classes, stretching classes, and usual self-care at relieving chronic low-back pain in a randomized controlled trial involving 228 adults residing in six cities in Western Washington. They hypothesized that yoga would prove superior to the other two interventions, because all eight clinical trials of yoga for this indication in the literature have shown it to be effective. However, the eight studies also had "considerable limitations," including small sample sizes, high attrition rates, and inconsistencies in the types of yoga provided, hours of class time, frequency of classes, and types of control situations.

In this trial, both yoga and stretching classes were held weekly for 75 minutes at Group Health facilities, for a total of 12 weeks. Patients were given CDs or DVDs to assist with home practice and were advised to practice 20 minutes on days when they weren’t attending class.

Patients were assessed via telephone interviews at baseline, 6 weeks, 12 weeks, and 26 weeks. The primary end point was self-rating at 26 weeks on the 23-item Roland-Morris Disability Questionnaire and on a scale of the bothersomeness of lower-back symptoms.

The yoga intervention (92 subjects) included breathing exercises, the use of 5-11 postures for 45-50 minutes (with adaptations allowed for patients’ limitations), and guided deep relaxation. Instructors had at least 500 hours of Viniyoga training and 5 years of teaching experience and were briefed by a study consultant who had expertise in low-back pain.

The stretching intervention (91 subjects) included aerobic activity, 10 strengthening exercises and 12 stretches held for 30 seconds each, and 52 minutes of 15 exercises that stretched all the major muscle groups but focused on the trunk and legs. Instructors were licensed physical therapists who had experience teaching classes and had completed a 2-hour training program for the study.

For the usual-care control condition (45 subjects), patients were given "The Back Pain Helpbook," which details the causes of back pain and makes recommendations regarding exercise, modifying lifestyle factors that contribute to back pain, and managing flares of back pain.

Back-related dysfunction declined over time in all three study groups, but the reduction was significantly greater with the yoga intervention and the stretching intervention. Contrary to their hypothesis, yoga classes did not prove superior to conventional stretching classes in this regard, Dr. Sherman and her colleagues said (Arch. Intern. Med. 2011 Oct. 24 [doi:10.1001/archinternmed.2011.524]).

Self-ratings of symptom bothersomeness did not differ significantly among the three groups.

Significantly more patients participating in both classes showed "substantial" (50% or more) clinical improvement from baseline: 52% of the yoga subjects and 56% of the stretching subjects reported this outcome, compared with only 23% of the control subjects.

Compared with the control group, both intervention groups were significantly more likely to describe their back pain as "better," "much better," or "completely gone" at all follow-up assessments, and were more likely to report they were "very satisfied" with their care.

The finding of such similar outcomes between the yoga group and the stretching group "suggests that yoga’s benefits were largely attributable to the physical benefits of stretching and strengthening the muscles and not to its mental components," the investigators said.

Thirteen patients (14%) in each intervention group reported mild or moderate adverse events that were possibly related to treatment, compared with only 1 control subject (0.02%).

Overall, the results of this study indicate that both yoga and stretching exercises are "reasonable treatment options for persons who are willing to engage in physical activities to relieve moderately impairing back pain," the researchers said.

This study was funded by the National Center for Complementary and Alternative Medicine. No relevant financial disclosures were reported by the authors.

Variants of three genes related to clopidogrel metabolism and platelet receptor function – CYP2C19, ABCB1, and ITGB3 – appear to be independent risk factors for early stent thrombosis, beyond the already known clinical and angiographic risk factors, according to a report in the Oct. 26 issue of JAMA.

A risk-prediction model that incorporated both genetic and clinical data had greater sensitivity and specificity at predicting early stent thrombosis than did a clinical model alone, said Dr. Guillaume Cayla of Institut de Cardiologie, INSERM Unite Mixte de Recherche, Salpetriere Hospital, Paris, and his associates.

The researchers assessed all of the 23 genetic variants that have been reported to correlate with clopidogrel pharmacogenetics and arterial thrombosis to determine which ones contribute most to early stent thrombosis.

They used a nationwide French registry of patients who had definite stent thrombosis within 30 days of implantation to identify 123 cases, then matched these for age and sex with 246 control subjects who had no stent thrombosis. Peripheral blood samples from these 369 subjects were genotyped for the suspect genetic variations.

Only four variations in three genes were found to be significantly associated with early stent thrombosis.

First, the CYP2C19 loss-of-function allele occurred in 49% of cases but only 26% of controls. Second, the CYP2C19 gain-of-function allele occurred in only 20% of cases but in 33% of controls. These findings strengthen the current evidence that CYP2C19 plays a predominant role in clopidogrel metabolism, Dr. Cayla and his colleagues said.

"The effects of different genes according to different ethnic groups may warrant dedicated studies."

Third, an ABCB1 variant occurred in 32% of cases but only 19% of controls. "The ABCB1 gene encodes a drug efflux transporter, P-glycoprotein, that modulates clopidogrel absorption. It has been previously associated with reduced clopidogrel response, but with variable clinical consequences," they noted.

And fourth, an ITGB3 variant occurred in only 16% of cases but 28% of controls. The ITGB3 gene encodes for integrin beta-3, "a component of the glycoprotein IIb/IIIa platelet receptor, which mediates the final pathway of platelet aggregation," they said.

There was a dose-response relationship in that risk of early stent thrombosis climbed steadily with carriage of an increasing number of these risk alleles, the investigators said.

A risk-prediction model that combined genetic data with clinical data had significantly greater power to predict early stent thrombosis than did a clinical model alone. The combined model had 67% sensitivity and 79% specificity in this regard, compared with 60% sensitivity and 70% specificity for the model using only clinical data.

"Patients in the highest tertile of risk using the combined clinical and genetic model had a sevenfold increased risk of early stent thrombosis vs. patients in the lowest tertile," Dr. Cayla and his associates said (JAMA 2011;306:1765-74).

The researchers also found that two nongenetic factors – loading dose of clopidogrel and the concomitant use of proton pump inhibitors (PPIs) – were significantly related to early stent thrombosis. Cases were much more likely than controls to have received a low loading dose of clopidogrel at stent implantation. And cases also were much more likely than controls to be taking PPIs, which have been suspected of interfering with clopidogrel metabolism.

Unlike the genetic risk factors, both clopidogrel dose and PPI use are modifiable risk factors, they noted.

This study was limited in that patients with the most severe early stent thrombosis died before they could be included in the study, so the genotype-phenotype relation remains unknown for them. "Stent malappositions or underexpansions are other important factors associated with stent thrombosis that were not evaluated," the investigators said.

In addition, the study findings may apply only to white patients because virtually all the subjects, who were drawn from the general population in France, were white. "The effects of different genes according to different ethnic groups may warrant dedicated studies," they added.

This study was funded by ACTION, the Société Francaise de Cardiologie, the Fédération Francaise de Cardiologie, and INSERM. The French registry of patients with early stent thrombosis was partially supported by Eli Lilly and the SGAM Foundation. Dr. Cayla and his associates reported ties to numerous industry sources.

Variants of three genes related to clopidogrel metabolism and platelet receptor function – CYP2C19, ABCB1, and ITGB3 – appear to be independent risk factors for early stent thrombosis, beyond the already known clinical and angiographic risk factors, according to a report in the Oct. 26 issue of JAMA.

A risk-prediction model that incorporated both genetic and clinical data had greater sensitivity and specificity at predicting early stent thrombosis than did a clinical model alone, said Dr. Guillaume Cayla of Institut de Cardiologie, INSERM Unite Mixte de Recherche, Salpetriere Hospital, Paris, and his associates.

The researchers assessed all of the 23 genetic variants that have been reported to correlate with clopidogrel pharmacogenetics and arterial thrombosis to determine which ones contribute most to early stent thrombosis.

They used a nationwide French registry of patients who had definite stent thrombosis within 30 days of implantation to identify 123 cases, then matched these for age and sex with 246 control subjects who had no stent thrombosis. Peripheral blood samples from these 369 subjects were genotyped for the suspect genetic variations.

Only four variations in three genes were found to be significantly associated with early stent thrombosis.

First, the CYP2C19 loss-of-function allele occurred in 49% of cases but only 26% of controls. Second, the CYP2C19 gain-of-function allele occurred in only 20% of cases but in 33% of controls. These findings strengthen the current evidence that CYP2C19 plays a predominant role in clopidogrel metabolism, Dr. Cayla and his colleagues said.

"The effects of different genes according to different ethnic groups may warrant dedicated studies."

Third, an ABCB1 variant occurred in 32% of cases but only 19% of controls. "The ABCB1 gene encodes a drug efflux transporter, P-glycoprotein, that modulates clopidogrel absorption. It has been previously associated with reduced clopidogrel response, but with variable clinical consequences," they noted.

And fourth, an ITGB3 variant occurred in only 16% of cases but 28% of controls. The ITGB3 gene encodes for integrin beta-3, "a component of the glycoprotein IIb/IIIa platelet receptor, which mediates the final pathway of platelet aggregation," they said.

There was a dose-response relationship in that risk of early stent thrombosis climbed steadily with carriage of an increasing number of these risk alleles, the investigators said.

A risk-prediction model that combined genetic data with clinical data had significantly greater power to predict early stent thrombosis than did a clinical model alone. The combined model had 67% sensitivity and 79% specificity in this regard, compared with 60% sensitivity and 70% specificity for the model using only clinical data.

"Patients in the highest tertile of risk using the combined clinical and genetic model had a sevenfold increased risk of early stent thrombosis vs. patients in the lowest tertile," Dr. Cayla and his associates said (JAMA 2011;306:1765-74).

The researchers also found that two nongenetic factors – loading dose of clopidogrel and the concomitant use of proton pump inhibitors (PPIs) – were significantly related to early stent thrombosis. Cases were much more likely than controls to have received a low loading dose of clopidogrel at stent implantation. And cases also were much more likely than controls to be taking PPIs, which have been suspected of interfering with clopidogrel metabolism.

Unlike the genetic risk factors, both clopidogrel dose and PPI use are modifiable risk factors, they noted.

This study was limited in that patients with the most severe early stent thrombosis died before they could be included in the study, so the genotype-phenotype relation remains unknown for them. "Stent malappositions or underexpansions are other important factors associated with stent thrombosis that were not evaluated," the investigators said.

In addition, the study findings may apply only to white patients because virtually all the subjects, who were drawn from the general population in France, were white. "The effects of different genes according to different ethnic groups may warrant dedicated studies," they added.

This study was funded by ACTION, the Société Francaise de Cardiologie, the Fédération Francaise de Cardiologie, and INSERM. The French registry of patients with early stent thrombosis was partially supported by Eli Lilly and the SGAM Foundation. Dr. Cayla and his associates reported ties to numerous industry sources.

Variants of three genes related to clopidogrel metabolism and platelet receptor function – CYP2C19, ABCB1, and ITGB3 – appear to be independent risk factors for early stent thrombosis, beyond the already known clinical and angiographic risk factors, according to a report in the Oct. 26 issue of JAMA.

A risk-prediction model that incorporated both genetic and clinical data had greater sensitivity and specificity at predicting early stent thrombosis than did a clinical model alone, said Dr. Guillaume Cayla of Institut de Cardiologie, INSERM Unite Mixte de Recherche, Salpetriere Hospital, Paris, and his associates.

The researchers assessed all of the 23 genetic variants that have been reported to correlate with clopidogrel pharmacogenetics and arterial thrombosis to determine which ones contribute most to early stent thrombosis.

They used a nationwide French registry of patients who had definite stent thrombosis within 30 days of implantation to identify 123 cases, then matched these for age and sex with 246 control subjects who had no stent thrombosis. Peripheral blood samples from these 369 subjects were genotyped for the suspect genetic variations.

Only four variations in three genes were found to be significantly associated with early stent thrombosis.

First, the CYP2C19 loss-of-function allele occurred in 49% of cases but only 26% of controls. Second, the CYP2C19 gain-of-function allele occurred in only 20% of cases but in 33% of controls. These findings strengthen the current evidence that CYP2C19 plays a predominant role in clopidogrel metabolism, Dr. Cayla and his colleagues said.

"The effects of different genes according to different ethnic groups may warrant dedicated studies."

Third, an ABCB1 variant occurred in 32% of cases but only 19% of controls. "The ABCB1 gene encodes a drug efflux transporter, P-glycoprotein, that modulates clopidogrel absorption. It has been previously associated with reduced clopidogrel response, but with variable clinical consequences," they noted.

And fourth, an ITGB3 variant occurred in only 16% of cases but 28% of controls. The ITGB3 gene encodes for integrin beta-3, "a component of the glycoprotein IIb/IIIa platelet receptor, which mediates the final pathway of platelet aggregation," they said.

There was a dose-response relationship in that risk of early stent thrombosis climbed steadily with carriage of an increasing number of these risk alleles, the investigators said.

A risk-prediction model that combined genetic data with clinical data had significantly greater power to predict early stent thrombosis than did a clinical model alone. The combined model had 67% sensitivity and 79% specificity in this regard, compared with 60% sensitivity and 70% specificity for the model using only clinical data.

"Patients in the highest tertile of risk using the combined clinical and genetic model had a sevenfold increased risk of early stent thrombosis vs. patients in the lowest tertile," Dr. Cayla and his associates said (JAMA 2011;306:1765-74).

The researchers also found that two nongenetic factors – loading dose of clopidogrel and the concomitant use of proton pump inhibitors (PPIs) – were significantly related to early stent thrombosis. Cases were much more likely than controls to have received a low loading dose of clopidogrel at stent implantation. And cases also were much more likely than controls to be taking PPIs, which have been suspected of interfering with clopidogrel metabolism.

Unlike the genetic risk factors, both clopidogrel dose and PPI use are modifiable risk factors, they noted.

This study was limited in that patients with the most severe early stent thrombosis died before they could be included in the study, so the genotype-phenotype relation remains unknown for them. "Stent malappositions or underexpansions are other important factors associated with stent thrombosis that were not evaluated," the investigators said.

In addition, the study findings may apply only to white patients because virtually all the subjects, who were drawn from the general population in France, were white. "The effects of different genes according to different ethnic groups may warrant dedicated studies," they added.

This study was funded by ACTION, the Société Francaise de Cardiologie, the Fédération Francaise de Cardiologie, and INSERM. The French registry of patients with early stent thrombosis was partially supported by Eli Lilly and the SGAM Foundation. Dr. Cayla and his associates reported ties to numerous industry sources.