Mary Ann Moon

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2010.06.072).

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society’s epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50-74 years at baseline in 1992-93 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11-15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said.

They also suggest that the use of insulin probably doesn’t raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2010.06.072).

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society’s epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50-74 years at baseline in 1992-93 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11-15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said.

They also suggest that the use of insulin probably doesn’t raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2010.06.072).

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society’s epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50-74 years at baseline in 1992-93 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11-15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said.

They also suggest that the use of insulin probably doesn’t raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.

An aromatase inhibitor should be considered as adjuvant therapy for all postmenopausal women with hormone receptor–positive breast cancer, according to an updated American Society of Clinical Oncology clinical practice guideline.

The optimal timing and duration of aromatase inhibitor (AI) treatment are not yet resolved, but it appears to reduce the risk of recurrence when taken at some time during adjuvant therapy – either alone as monotherapy, as sequential therapy before tamoxifen therapy commences or after 2-3 years of tamoxifen treatment, or as extended therapy after 5 years of tamoxifen is completed, said Dr. Harold J. Burstein of the Dana-Farber Cancer Institute, Boston, and his associates on ASCO's Endocrine Therapy for Breast Cancer Update Committee.

The last update on the adjuvant use of AIs for hormone receptor–positive breast cancer was published in 2004. “Our panel carefully reviewed the explosion of research that has emerged in the past 5 years on anti-estrogen drugs, and filled in gaps in our understanding of how best to use these newer treatments, and what the trade-offs and side effects of therapy would be,” Dr. Burstein noted in a press statement.

Their review focused on 12 prospective randomized clinical trials gleaned from 484 articles or abstracts from the medical literature, presentations, or posters.

The data are somewhat limited. Most of the studies had relatively short follow-up times, and the longest median follow-up was only 8 years. Because of that and patients' generally favorable prognoses, few breast cancer events occurred during follow-up.

In addition, the assessment of important subgroups of patients was limited by relatively small sample sizes, and the small samples also limited analysis of quality-of-life data, Dr. Burstein and his colleagues said (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756]).

Among the major findings:

▸ Adding an AI to adjuvant therapy improves disease-free survival and reduces the risk of distant metastasis, locoregional recurrence, and contralateral breast cancer. The reduction is modest – typically less than 5% over several years – but these outcomes are clinically important to patients. Only a few trials demonstrated a statistically significant increase in overall survival.

▸ AI therapy should not extend beyond 5 years, as either initial or extended adjuvant treatment, because results on longer-term treatment are not yet available.

▸ The optimal length of time before switching from tamoxifen to an AI is not yet known. For sequential treatment, patients should receive an AI after 2-3 years of tamoxifen, for a total of 5 years of adjuvant endocrine therapy. Alternatively, patients who begin an AI but discontinue it before 5 years have elapsed can consider taking tamoxifen until a total of 5 years of endocrine therapy accrue. For extended therapy, patients can be offered an AI after they have taken 5 years of tamoxifen. The data on extended therapy, however, are not as extensive as with sequential therapy.

▸ As of now, no clinically important differences in effectiveness have been reported among the three commercially available AIs (anastrozole, letrozole, and exemestane).

▸ Research to date has not revealed a specific marker that identifies patients most likely to benefit from AI therapy, nor a clinical subset of patients most likely to benefit.

▸ AIs generally are well tolerated. The drugs have been linked to increased risk of hypercholesterolemia and hypertension, and possibly of cardiovascular disease, but longer follow-up is needed to determine potential CV toxicity.

AIs also often cause a mild to moderate musculoskeletal/arthralgia syndrome. They have been associated with a greater loss of bone mineral density and a 2%-4% increased risk of fracture, compared with tamoxifen, but the long-term impact of treatment on bone is not yet known.

AIs appear to have fewer gynecologic adverse effects than tamoxifen. An increased risk of uterine cancer, benign endometrial pathology, hysterectomy, and vaginal discharge has not yet been noted with AIs, as it has with tamoxifen. AIs may produce fewer hot flashes and less vaginal dryness than tamoxifen.

The committee stressed that the late effects of AI therapy, as well as the possible adverse effects of extended AI therapy, have not yet been fully characterized.

The committee also noted that there is no evidence yet for or against the usefulness of AI therapy in men with breast cancer.

To facilitate treatment adherence, the updated guideline emphasized that clinicians should alert patients to common adverse effects and potential toxicities of AIs. Research shows that up to 40% of patients discontinue tamoxifen within 3 years and half do so within 5 years, and the findings with AIs are similar. The clear majority of patients who stop treatment prematurely do so because of adverse effects.

In particular, the musculoskeletal effects of AIs prompted discontinuation in more than 10% of women in one study. “Information support for patients about anticipated adverse effects and management of those adverse effects may increase persistence,” according to the guideline.

Monetary constraints are another cause of nonadherence. In one study of tamoxifen, 60% of patients who discontinued treatment early said that the cost of the drug was a key factor. “It is likely that the out-of-pocket costs of AIs pose an even greater barrier to patients,” the committee said.

The complete clinical practice guideline is available at www.asco.org/guidelines/endocrinebreastwww.cancer.net

Disclosures: Some of the update committee members reported ties to Pfizer, Novartis, and AstraZeneca.

An aromatase inhibitor should be considered as adjuvant therapy for all postmenopausal women with hormone receptor–positive breast cancer, according to an updated American Society of Clinical Oncology clinical practice guideline.

The optimal timing and duration of aromatase inhibitor (AI) treatment are not yet resolved, but it appears to reduce the risk of recurrence when taken at some time during adjuvant therapy – either alone as monotherapy, as sequential therapy before tamoxifen therapy commences or after 2-3 years of tamoxifen treatment, or as extended therapy after 5 years of tamoxifen is completed, said Dr. Harold J. Burstein of the Dana-Farber Cancer Institute, Boston, and his associates on ASCO's Endocrine Therapy for Breast Cancer Update Committee.

The last update on the adjuvant use of AIs for hormone receptor–positive breast cancer was published in 2004. “Our panel carefully reviewed the explosion of research that has emerged in the past 5 years on anti-estrogen drugs, and filled in gaps in our understanding of how best to use these newer treatments, and what the trade-offs and side effects of therapy would be,” Dr. Burstein noted in a press statement.

Their review focused on 12 prospective randomized clinical trials gleaned from 484 articles or abstracts from the medical literature, presentations, or posters.

The data are somewhat limited. Most of the studies had relatively short follow-up times, and the longest median follow-up was only 8 years. Because of that and patients' generally favorable prognoses, few breast cancer events occurred during follow-up.

In addition, the assessment of important subgroups of patients was limited by relatively small sample sizes, and the small samples also limited analysis of quality-of-life data, Dr. Burstein and his colleagues said (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756]).

Among the major findings:

▸ Adding an AI to adjuvant therapy improves disease-free survival and reduces the risk of distant metastasis, locoregional recurrence, and contralateral breast cancer. The reduction is modest – typically less than 5% over several years – but these outcomes are clinically important to patients. Only a few trials demonstrated a statistically significant increase in overall survival.

▸ AI therapy should not extend beyond 5 years, as either initial or extended adjuvant treatment, because results on longer-term treatment are not yet available.

▸ The optimal length of time before switching from tamoxifen to an AI is not yet known. For sequential treatment, patients should receive an AI after 2-3 years of tamoxifen, for a total of 5 years of adjuvant endocrine therapy. Alternatively, patients who begin an AI but discontinue it before 5 years have elapsed can consider taking tamoxifen until a total of 5 years of endocrine therapy accrue. For extended therapy, patients can be offered an AI after they have taken 5 years of tamoxifen. The data on extended therapy, however, are not as extensive as with sequential therapy.

▸ As of now, no clinically important differences in effectiveness have been reported among the three commercially available AIs (anastrozole, letrozole, and exemestane).

▸ Research to date has not revealed a specific marker that identifies patients most likely to benefit from AI therapy, nor a clinical subset of patients most likely to benefit.

▸ AIs generally are well tolerated. The drugs have been linked to increased risk of hypercholesterolemia and hypertension, and possibly of cardiovascular disease, but longer follow-up is needed to determine potential CV toxicity.

AIs also often cause a mild to moderate musculoskeletal/arthralgia syndrome. They have been associated with a greater loss of bone mineral density and a 2%-4% increased risk of fracture, compared with tamoxifen, but the long-term impact of treatment on bone is not yet known.

AIs appear to have fewer gynecologic adverse effects than tamoxifen. An increased risk of uterine cancer, benign endometrial pathology, hysterectomy, and vaginal discharge has not yet been noted with AIs, as it has with tamoxifen. AIs may produce fewer hot flashes and less vaginal dryness than tamoxifen.

The committee stressed that the late effects of AI therapy, as well as the possible adverse effects of extended AI therapy, have not yet been fully characterized.

The committee also noted that there is no evidence yet for or against the usefulness of AI therapy in men with breast cancer.

To facilitate treatment adherence, the updated guideline emphasized that clinicians should alert patients to common adverse effects and potential toxicities of AIs. Research shows that up to 40% of patients discontinue tamoxifen within 3 years and half do so within 5 years, and the findings with AIs are similar. The clear majority of patients who stop treatment prematurely do so because of adverse effects.

In particular, the musculoskeletal effects of AIs prompted discontinuation in more than 10% of women in one study. “Information support for patients about anticipated adverse effects and management of those adverse effects may increase persistence,” according to the guideline.

Monetary constraints are another cause of nonadherence. In one study of tamoxifen, 60% of patients who discontinued treatment early said that the cost of the drug was a key factor. “It is likely that the out-of-pocket costs of AIs pose an even greater barrier to patients,” the committee said.

The complete clinical practice guideline is available at www.asco.org/guidelines/endocrinebreastwww.cancer.net

Disclosures: Some of the update committee members reported ties to Pfizer, Novartis, and AstraZeneca.

An aromatase inhibitor should be considered as adjuvant therapy for all postmenopausal women with hormone receptor–positive breast cancer, according to an updated American Society of Clinical Oncology clinical practice guideline.

The optimal timing and duration of aromatase inhibitor (AI) treatment are not yet resolved, but it appears to reduce the risk of recurrence when taken at some time during adjuvant therapy – either alone as monotherapy, as sequential therapy before tamoxifen therapy commences or after 2-3 years of tamoxifen treatment, or as extended therapy after 5 years of tamoxifen is completed, said Dr. Harold J. Burstein of the Dana-Farber Cancer Institute, Boston, and his associates on ASCO's Endocrine Therapy for Breast Cancer Update Committee.

The last update on the adjuvant use of AIs for hormone receptor–positive breast cancer was published in 2004. “Our panel carefully reviewed the explosion of research that has emerged in the past 5 years on anti-estrogen drugs, and filled in gaps in our understanding of how best to use these newer treatments, and what the trade-offs and side effects of therapy would be,” Dr. Burstein noted in a press statement.

Their review focused on 12 prospective randomized clinical trials gleaned from 484 articles or abstracts from the medical literature, presentations, or posters.

The data are somewhat limited. Most of the studies had relatively short follow-up times, and the longest median follow-up was only 8 years. Because of that and patients' generally favorable prognoses, few breast cancer events occurred during follow-up.

In addition, the assessment of important subgroups of patients was limited by relatively small sample sizes, and the small samples also limited analysis of quality-of-life data, Dr. Burstein and his colleagues said (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756]).

Among the major findings:

▸ Adding an AI to adjuvant therapy improves disease-free survival and reduces the risk of distant metastasis, locoregional recurrence, and contralateral breast cancer. The reduction is modest – typically less than 5% over several years – but these outcomes are clinically important to patients. Only a few trials demonstrated a statistically significant increase in overall survival.

▸ AI therapy should not extend beyond 5 years, as either initial or extended adjuvant treatment, because results on longer-term treatment are not yet available.

▸ The optimal length of time before switching from tamoxifen to an AI is not yet known. For sequential treatment, patients should receive an AI after 2-3 years of tamoxifen, for a total of 5 years of adjuvant endocrine therapy. Alternatively, patients who begin an AI but discontinue it before 5 years have elapsed can consider taking tamoxifen until a total of 5 years of endocrine therapy accrue. For extended therapy, patients can be offered an AI after they have taken 5 years of tamoxifen. The data on extended therapy, however, are not as extensive as with sequential therapy.

▸ As of now, no clinically important differences in effectiveness have been reported among the three commercially available AIs (anastrozole, letrozole, and exemestane).

▸ Research to date has not revealed a specific marker that identifies patients most likely to benefit from AI therapy, nor a clinical subset of patients most likely to benefit.

▸ AIs generally are well tolerated. The drugs have been linked to increased risk of hypercholesterolemia and hypertension, and possibly of cardiovascular disease, but longer follow-up is needed to determine potential CV toxicity.

AIs also often cause a mild to moderate musculoskeletal/arthralgia syndrome. They have been associated with a greater loss of bone mineral density and a 2%-4% increased risk of fracture, compared with tamoxifen, but the long-term impact of treatment on bone is not yet known.

AIs appear to have fewer gynecologic adverse effects than tamoxifen. An increased risk of uterine cancer, benign endometrial pathology, hysterectomy, and vaginal discharge has not yet been noted with AIs, as it has with tamoxifen. AIs may produce fewer hot flashes and less vaginal dryness than tamoxifen.

The committee stressed that the late effects of AI therapy, as well as the possible adverse effects of extended AI therapy, have not yet been fully characterized.

The committee also noted that there is no evidence yet for or against the usefulness of AI therapy in men with breast cancer.

To facilitate treatment adherence, the updated guideline emphasized that clinicians should alert patients to common adverse effects and potential toxicities of AIs. Research shows that up to 40% of patients discontinue tamoxifen within 3 years and half do so within 5 years, and the findings with AIs are similar. The clear majority of patients who stop treatment prematurely do so because of adverse effects.

In particular, the musculoskeletal effects of AIs prompted discontinuation in more than 10% of women in one study. “Information support for patients about anticipated adverse effects and management of those adverse effects may increase persistence,” according to the guideline.

Monetary constraints are another cause of nonadherence. In one study of tamoxifen, 60% of patients who discontinued treatment early said that the cost of the drug was a key factor. “It is likely that the out-of-pocket costs of AIs pose an even greater barrier to patients,” the committee said.

The complete clinical practice guideline is available at www.asco.org/guidelines/endocrinebreastwww.cancer.net

Disclosures: Some of the update committee members reported ties to Pfizer, Novartis, and AstraZeneca.

Among births that occur during the term and postterm range of 37-44 weeks' gestation, the risk of cerebral palsy is lowest at 40 weeks and highest at the “early” extreme of 37-38 weeks and the “late” extreme of 42 weeks or more, said Dr. Dag Moster of the University of Bergen, Norway, and his associates.

Preterm delivery is a well-established risk factor for CP, but there is scant information on CP risk within the term range, even though most cases of CP occur in children born at term. Dr. Moster and his colleagues examined the issue using data in a nationwide Norwegian registry covering 1,682,441 singleton live births at 37-44 weeks that took place between 1967 and 2001, as well as a medical registry of all the disabled people in the country born during the same period.

There were 1,938 infants in this cohort who were eventually diagnosed as having CP, for an overall prevalence of 1.15 cases per 1,000 live births (JAMA 2010;304:976-82). Delivery at 40 weeks was associated with the lowest CP risk, with a prevalence of 0.99 cases per 1,000 live births.

In comparison, the prevalence of CP at 37 weeks' gestation was 1.91 per 1,000 (for a relative risk of 1.9) and at 38 weeks was 1.25 per 1,000 (for a relative risk of 1.3). Similarly, the prevalence of CP at 42 weeks was 1.36 per 1,000 live births (for a relative risk of 1.4) and after 42 weeks was 1.44 per 1,000 live births (for a relative risk of 1.4).

Children with CP had lower mean birth weights (3,437 g) compared with children without CP (3,585 g) and smaller head circumferences (35.1 cm) compared with children without CP (35.3 cm). Children with CP were 82 times more likely to have had low Apgar scores (less than 4) and were eight times more likely to have been transferred to pediatric units after delivery. Results were essentially the same in a further analysis of the data after adjustment for possible confounders such as maternal age, marital status, and education level.

“One possible interpretation is that delivery too early or too late, even within the limited range of term and postterm births, increases the risk of CP.

“However, an equally plausible interpretation is that fetuses predisposed to CP have a disturbance in the timing of their delivery, which causes them to be more often delivered early or late,” Dr. Moster and his associates said.

“This apparently happens with other fetal conditions: There is a U-shaped pattern in the risk of congenital anomalies with gestational age after 37 weeks. Since congenital anomalies are not caused by the timing of delivery, the most plausible explanation is reverse causation: Malformed infants experience disruptions in their time of delivery, with increased chance of delivery either earlier or later than 40 weeks,” the researchers said.

“Although the forces that regulate timing of a normal delivery are poorly understood, it appears that the types of malformations most likely to disrupt the timing of delivery often involve cerebral function.

For example, anencephalic fetuses have a tendency to be born post term, children with Trisomy 18 to be born preterm or post term, and children with Down syndrome to be born early.

“It is possible that cerebral damage later expressed as CP similarly disrupts time of delivery,” Dr. Moster and his associates said.

The lower birth weight and smaller head circumference among CP cases in this cohort “suggest that these children differ from non-CP infants even before birth,” they added.

Dr. Moster and his associates emphasized that it would be incorrect to extrapolate from these study findings that intervening to alter the time of delivery could reduce the rate of CP.

Disclosures: This study was sponsored by the National Institutes of Health, the National Institute of Environmental Health Sciences, the Unger-Vetlesen Charitable Fund, the U.S.-Norway Fulbright Foundation, the Norwegian Society of Pediatricians, the University of Bergen, and the Research Council of Norway. No financial conflicts of interest were reported.

Among births that occur during the term and postterm range of 37-44 weeks' gestation, the risk of cerebral palsy is lowest at 40 weeks and highest at the “early” extreme of 37-38 weeks and the “late” extreme of 42 weeks or more, said Dr. Dag Moster of the University of Bergen, Norway, and his associates.

Preterm delivery is a well-established risk factor for CP, but there is scant information on CP risk within the term range, even though most cases of CP occur in children born at term. Dr. Moster and his colleagues examined the issue using data in a nationwide Norwegian registry covering 1,682,441 singleton live births at 37-44 weeks that took place between 1967 and 2001, as well as a medical registry of all the disabled people in the country born during the same period.

There were 1,938 infants in this cohort who were eventually diagnosed as having CP, for an overall prevalence of 1.15 cases per 1,000 live births (JAMA 2010;304:976-82). Delivery at 40 weeks was associated with the lowest CP risk, with a prevalence of 0.99 cases per 1,000 live births.

In comparison, the prevalence of CP at 37 weeks' gestation was 1.91 per 1,000 (for a relative risk of 1.9) and at 38 weeks was 1.25 per 1,000 (for a relative risk of 1.3). Similarly, the prevalence of CP at 42 weeks was 1.36 per 1,000 live births (for a relative risk of 1.4) and after 42 weeks was 1.44 per 1,000 live births (for a relative risk of 1.4).

Children with CP had lower mean birth weights (3,437 g) compared with children without CP (3,585 g) and smaller head circumferences (35.1 cm) compared with children without CP (35.3 cm). Children with CP were 82 times more likely to have had low Apgar scores (less than 4) and were eight times more likely to have been transferred to pediatric units after delivery. Results were essentially the same in a further analysis of the data after adjustment for possible confounders such as maternal age, marital status, and education level.

“One possible interpretation is that delivery too early or too late, even within the limited range of term and postterm births, increases the risk of CP.

“However, an equally plausible interpretation is that fetuses predisposed to CP have a disturbance in the timing of their delivery, which causes them to be more often delivered early or late,” Dr. Moster and his associates said.

“This apparently happens with other fetal conditions: There is a U-shaped pattern in the risk of congenital anomalies with gestational age after 37 weeks. Since congenital anomalies are not caused by the timing of delivery, the most plausible explanation is reverse causation: Malformed infants experience disruptions in their time of delivery, with increased chance of delivery either earlier or later than 40 weeks,” the researchers said.

“Although the forces that regulate timing of a normal delivery are poorly understood, it appears that the types of malformations most likely to disrupt the timing of delivery often involve cerebral function.

For example, anencephalic fetuses have a tendency to be born post term, children with Trisomy 18 to be born preterm or post term, and children with Down syndrome to be born early.

“It is possible that cerebral damage later expressed as CP similarly disrupts time of delivery,” Dr. Moster and his associates said.

The lower birth weight and smaller head circumference among CP cases in this cohort “suggest that these children differ from non-CP infants even before birth,” they added.

Dr. Moster and his associates emphasized that it would be incorrect to extrapolate from these study findings that intervening to alter the time of delivery could reduce the rate of CP.

Disclosures: This study was sponsored by the National Institutes of Health, the National Institute of Environmental Health Sciences, the Unger-Vetlesen Charitable Fund, the U.S.-Norway Fulbright Foundation, the Norwegian Society of Pediatricians, the University of Bergen, and the Research Council of Norway. No financial conflicts of interest were reported.

Among births that occur during the term and postterm range of 37-44 weeks' gestation, the risk of cerebral palsy is lowest at 40 weeks and highest at the “early” extreme of 37-38 weeks and the “late” extreme of 42 weeks or more, said Dr. Dag Moster of the University of Bergen, Norway, and his associates.

Preterm delivery is a well-established risk factor for CP, but there is scant information on CP risk within the term range, even though most cases of CP occur in children born at term. Dr. Moster and his colleagues examined the issue using data in a nationwide Norwegian registry covering 1,682,441 singleton live births at 37-44 weeks that took place between 1967 and 2001, as well as a medical registry of all the disabled people in the country born during the same period.

There were 1,938 infants in this cohort who were eventually diagnosed as having CP, for an overall prevalence of 1.15 cases per 1,000 live births (JAMA 2010;304:976-82). Delivery at 40 weeks was associated with the lowest CP risk, with a prevalence of 0.99 cases per 1,000 live births.

In comparison, the prevalence of CP at 37 weeks' gestation was 1.91 per 1,000 (for a relative risk of 1.9) and at 38 weeks was 1.25 per 1,000 (for a relative risk of 1.3). Similarly, the prevalence of CP at 42 weeks was 1.36 per 1,000 live births (for a relative risk of 1.4) and after 42 weeks was 1.44 per 1,000 live births (for a relative risk of 1.4).

Children with CP had lower mean birth weights (3,437 g) compared with children without CP (3,585 g) and smaller head circumferences (35.1 cm) compared with children without CP (35.3 cm). Children with CP were 82 times more likely to have had low Apgar scores (less than 4) and were eight times more likely to have been transferred to pediatric units after delivery. Results were essentially the same in a further analysis of the data after adjustment for possible confounders such as maternal age, marital status, and education level.

“One possible interpretation is that delivery too early or too late, even within the limited range of term and postterm births, increases the risk of CP.

“However, an equally plausible interpretation is that fetuses predisposed to CP have a disturbance in the timing of their delivery, which causes them to be more often delivered early or late,” Dr. Moster and his associates said.

“This apparently happens with other fetal conditions: There is a U-shaped pattern in the risk of congenital anomalies with gestational age after 37 weeks. Since congenital anomalies are not caused by the timing of delivery, the most plausible explanation is reverse causation: Malformed infants experience disruptions in their time of delivery, with increased chance of delivery either earlier or later than 40 weeks,” the researchers said.

“Although the forces that regulate timing of a normal delivery are poorly understood, it appears that the types of malformations most likely to disrupt the timing of delivery often involve cerebral function.

For example, anencephalic fetuses have a tendency to be born post term, children with Trisomy 18 to be born preterm or post term, and children with Down syndrome to be born early.

“It is possible that cerebral damage later expressed as CP similarly disrupts time of delivery,” Dr. Moster and his associates said.

The lower birth weight and smaller head circumference among CP cases in this cohort “suggest that these children differ from non-CP infants even before birth,” they added.

Dr. Moster and his associates emphasized that it would be incorrect to extrapolate from these study findings that intervening to alter the time of delivery could reduce the rate of CP.

Disclosures: This study was sponsored by the National Institutes of Health, the National Institute of Environmental Health Sciences, the Unger-Vetlesen Charitable Fund, the U.S.-Norway Fulbright Foundation, the Norwegian Society of Pediatricians, the University of Bergen, and the Research Council of Norway. No financial conflicts of interest were reported.

Prophylactic counterpulsation with an intra-aortic balloon pump did not prevent major adverse cardiovascular events from developing in high-risk PCI patients, according to a randomized study of 294 patients in the United Kingdom.

In what they described as the first randomized controlled trial to assess the efficacy and safety of the prophylactic use of an IABP in patients at high risk due to severe left ventricular impairment and extensive coronary disease, investigators found no difference in cardiovascular events between patients randomly assigned to planned IABP counterpulsation and those assigned to no planned IABP counterpulsation before PCI.

In addition, “elective IABP use was associated with significantly fewer procedural complications but more minor bleeding and more access-site complications than when PCI was performed without planned IABP insertion,” said Dr. Divaka Perera of King's College, London, and his associates.

They performed the prospective, open-label trial at 17 interventional cardiology centers in the United Kingdom in 2005-2009. The study involved 294 patients with multivessel disease, impaired left ventricular function, and a large amount of myocardium subtended by stenosed vessels who were scheduled for PCI of either native coronary arteries or bypass grafts.

A total of 147 patients underwent IABP insertion before PCI and 147 had no IABP insertion unless the need for counterpulsation developed during PCI. All the subjects were followed until hospital discharge or for 28 days following the procedure.

Of the 147 patients in the control group who did not receive prophylactic IABP, 18 (12%) required rescue IABP counterpulsation during PCI, usually because they developed prolonged hypotension during the procedure (13 cases).

The primary end point of major adverse cardiac or cardiovascular events (MACCE) within 28 days occurred in 15% of the patients who had prophylactic placement of an IABP and 16% of those who did not, a nonsignificant difference. There was a 2.8% absolute decrease in mortality at 6 months with prophylactic IABP counterpulsation, but that difference also was nonsignificant, according to the researchers (JAMA 2010;304;867-74).

The MACCE rates also did not differ significantly in important subgroups of patients, including those who had impaired kidney function, diabetes, or extremely high risk of PCI-related complications.

Major procedural complications occurred less often in the group with prophylactic IABP (1.3%) than in the control group (10.7%), but bleeding events and access-site complications were more frequent with prophylactic IABP (19.2% vs. 11.3% and 3.3% vs. 0%, respectively).

“These results do not support a strategy of prophylactic placement of an intra-aortic balloon catheter during PCI in all patients with severe left ventricular dysfunction” and a high risk of PCI-related complications, Dr. Perera and his associates said.

Disclosures: The study was sponsored by the British Cardiovascular Intervention Society, funded by Maquet Cardiovascular, Cordis, and Johnson & Johnson, and was supported in part by Lilly. Dr. Perera and an associate received financial support from the U.K. Department of Health.

Prophylactic counterpulsation with an intra-aortic balloon pump did not prevent major adverse cardiovascular events from developing in high-risk PCI patients, according to a randomized study of 294 patients in the United Kingdom.

In what they described as the first randomized controlled trial to assess the efficacy and safety of the prophylactic use of an IABP in patients at high risk due to severe left ventricular impairment and extensive coronary disease, investigators found no difference in cardiovascular events between patients randomly assigned to planned IABP counterpulsation and those assigned to no planned IABP counterpulsation before PCI.

In addition, “elective IABP use was associated with significantly fewer procedural complications but more minor bleeding and more access-site complications than when PCI was performed without planned IABP insertion,” said Dr. Divaka Perera of King's College, London, and his associates.

They performed the prospective, open-label trial at 17 interventional cardiology centers in the United Kingdom in 2005-2009. The study involved 294 patients with multivessel disease, impaired left ventricular function, and a large amount of myocardium subtended by stenosed vessels who were scheduled for PCI of either native coronary arteries or bypass grafts.

A total of 147 patients underwent IABP insertion before PCI and 147 had no IABP insertion unless the need for counterpulsation developed during PCI. All the subjects were followed until hospital discharge or for 28 days following the procedure.

Of the 147 patients in the control group who did not receive prophylactic IABP, 18 (12%) required rescue IABP counterpulsation during PCI, usually because they developed prolonged hypotension during the procedure (13 cases).

The primary end point of major adverse cardiac or cardiovascular events (MACCE) within 28 days occurred in 15% of the patients who had prophylactic placement of an IABP and 16% of those who did not, a nonsignificant difference. There was a 2.8% absolute decrease in mortality at 6 months with prophylactic IABP counterpulsation, but that difference also was nonsignificant, according to the researchers (JAMA 2010;304;867-74).

The MACCE rates also did not differ significantly in important subgroups of patients, including those who had impaired kidney function, diabetes, or extremely high risk of PCI-related complications.

Major procedural complications occurred less often in the group with prophylactic IABP (1.3%) than in the control group (10.7%), but bleeding events and access-site complications were more frequent with prophylactic IABP (19.2% vs. 11.3% and 3.3% vs. 0%, respectively).

“These results do not support a strategy of prophylactic placement of an intra-aortic balloon catheter during PCI in all patients with severe left ventricular dysfunction” and a high risk of PCI-related complications, Dr. Perera and his associates said.

Disclosures: The study was sponsored by the British Cardiovascular Intervention Society, funded by Maquet Cardiovascular, Cordis, and Johnson & Johnson, and was supported in part by Lilly. Dr. Perera and an associate received financial support from the U.K. Department of Health.

Prophylactic counterpulsation with an intra-aortic balloon pump did not prevent major adverse cardiovascular events from developing in high-risk PCI patients, according to a randomized study of 294 patients in the United Kingdom.

In what they described as the first randomized controlled trial to assess the efficacy and safety of the prophylactic use of an IABP in patients at high risk due to severe left ventricular impairment and extensive coronary disease, investigators found no difference in cardiovascular events between patients randomly assigned to planned IABP counterpulsation and those assigned to no planned IABP counterpulsation before PCI.

In addition, “elective IABP use was associated with significantly fewer procedural complications but more minor bleeding and more access-site complications than when PCI was performed without planned IABP insertion,” said Dr. Divaka Perera of King's College, London, and his associates.

They performed the prospective, open-label trial at 17 interventional cardiology centers in the United Kingdom in 2005-2009. The study involved 294 patients with multivessel disease, impaired left ventricular function, and a large amount of myocardium subtended by stenosed vessels who were scheduled for PCI of either native coronary arteries or bypass grafts.

A total of 147 patients underwent IABP insertion before PCI and 147 had no IABP insertion unless the need for counterpulsation developed during PCI. All the subjects were followed until hospital discharge or for 28 days following the procedure.

Of the 147 patients in the control group who did not receive prophylactic IABP, 18 (12%) required rescue IABP counterpulsation during PCI, usually because they developed prolonged hypotension during the procedure (13 cases).

The primary end point of major adverse cardiac or cardiovascular events (MACCE) within 28 days occurred in 15% of the patients who had prophylactic placement of an IABP and 16% of those who did not, a nonsignificant difference. There was a 2.8% absolute decrease in mortality at 6 months with prophylactic IABP counterpulsation, but that difference also was nonsignificant, according to the researchers (JAMA 2010;304;867-74).

The MACCE rates also did not differ significantly in important subgroups of patients, including those who had impaired kidney function, diabetes, or extremely high risk of PCI-related complications.

Major procedural complications occurred less often in the group with prophylactic IABP (1.3%) than in the control group (10.7%), but bleeding events and access-site complications were more frequent with prophylactic IABP (19.2% vs. 11.3% and 3.3% vs. 0%, respectively).

“These results do not support a strategy of prophylactic placement of an intra-aortic balloon catheter during PCI in all patients with severe left ventricular dysfunction” and a high risk of PCI-related complications, Dr. Perera and his associates said.

Disclosures: The study was sponsored by the British Cardiovascular Intervention Society, funded by Maquet Cardiovascular, Cordis, and Johnson & Johnson, and was supported in part by Lilly. Dr. Perera and an associate received financial support from the U.K. Department of Health.

Vaccinating pregnant women against seasonal influenza reduced the risk of laboratory-confirmed influenza infection in their infants by 41%, according to a study.

Maternal immunization similarly cut by 39% the risk that infants up to 6 months of age would be hospitalized for influenza-like illness, said Angelia A. Eick, Ph.D., of the Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Influenza vaccination is already recommended for pregnant women to reduce their risk of developing flu-related complications. "These findings provide support for the added benefit of protecting infants from influenza virus infection up to 6 months, the period when infants are not eligible for influenza vaccination but are at highest risk of severe influenza illness," they noted.

Even though such immunization is recommended during pregnancy, it is not well accepted in the United States and many pregnant women do not get vaccinated. Since it would be unethical to perform a randomized, controlled study of maternal vaccination, Dr. Eick and her colleagues conducted a nonrandomized observational study to assess whether immunization during pregnancy conferred protection to infants.

The study subjects were 1,160 mother-infant pairs in which approximately half the mothers (573) had chosen to receive seasonal flu vaccine while pregnant and the other half (587) had declined the vaccine. All were enrolled after delivering healthy singleton infants at seven hospitals serving the Navajo and White Mountain Apache Indian reservations in the southwestern United States during three flu seasons between 2002 and 2005.

A total of 605 infants developed influenza-like illness during the flu season following delivery. "We found a 41% reduction in the risk of laboratory-confirmed influenza virus infection for infants of influenza-vaccinated mothers compared with infants of unvaccinated mothers," the researchers said (Arch. Pediatr. Adolesc. Med. 2010 [doi10.1001/archpediatrics.2010.192]).

The incidence of influenza-like illness was 6.7 per 1,000 person-days for infants of mothers who had been vaccinated, compared with 7.2 per 1,000 person-days for infants of mothers who had not.

Among the infants whose mothers were vaccinated, there was a 41% reduction in the risk of laboratory-confirmed influenza virus infection compared with those whose mothers declined vaccination.

When the analysis was restricted only to cases of influenza that required hospitalization, a 39% reduction in risk was found for infants of women who had been vaccinated, compared with those of mothers who had not been vaccinated.

Cord blood samples or infant blood samples taken at 2–3 months of age were available for 160 study subjects. In this subgroup, the risk of influenza infection declined with increasing antibody titers.

The exact mechanism by which vaccination of the mother conferred protection to the infant is not certain. It may be due to maternal influenza antibodies being acquired transplacentally or through breastfeeding, or to reduced infant exposure to influenza in the mother. It even could be due to residual confounding not accounted for in the statistical analyses, but the finding of significantly higher antibody titers in 2- to 3-month-old infants who did not develop illness argues against that possibility, Dr. Eick and her colleagues said.

The study was funded by the U.S. Department of Health and Human Services' National Vaccine Program Office, the Office of Minority and Women's Health (now the Office of Health Disparities), the Centers for Disease Control and Prevention, Aventis-Pasteur, and Evans-Powderject. One of Dr. Eick's associates reported ties with MedImmune, Pfizer, and Sanofi-Pasteur, all of which manufacture influenza vaccine.

Vaccinating pregnant women against seasonal influenza reduced the risk of laboratory-confirmed influenza infection in their infants by 41%, according to a study.

Maternal immunization similarly cut by 39% the risk that infants up to 6 months of age would be hospitalized for influenza-like illness, said Angelia A. Eick, Ph.D., of the Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Influenza vaccination is already recommended for pregnant women to reduce their risk of developing flu-related complications. "These findings provide support for the added benefit of protecting infants from influenza virus infection up to 6 months, the period when infants are not eligible for influenza vaccination but are at highest risk of severe influenza illness," they noted.

Even though such immunization is recommended during pregnancy, it is not well accepted in the United States and many pregnant women do not get vaccinated. Since it would be unethical to perform a randomized, controlled study of maternal vaccination, Dr. Eick and her colleagues conducted a nonrandomized observational study to assess whether immunization during pregnancy conferred protection to infants.

The study subjects were 1,160 mother-infant pairs in which approximately half the mothers (573) had chosen to receive seasonal flu vaccine while pregnant and the other half (587) had declined the vaccine. All were enrolled after delivering healthy singleton infants at seven hospitals serving the Navajo and White Mountain Apache Indian reservations in the southwestern United States during three flu seasons between 2002 and 2005.

A total of 605 infants developed influenza-like illness during the flu season following delivery. "We found a 41% reduction in the risk of laboratory-confirmed influenza virus infection for infants of influenza-vaccinated mothers compared with infants of unvaccinated mothers," the researchers said (Arch. Pediatr. Adolesc. Med. 2010 [doi10.1001/archpediatrics.2010.192]).

The incidence of influenza-like illness was 6.7 per 1,000 person-days for infants of mothers who had been vaccinated, compared with 7.2 per 1,000 person-days for infants of mothers who had not.

Among the infants whose mothers were vaccinated, there was a 41% reduction in the risk of laboratory-confirmed influenza virus infection compared with those whose mothers declined vaccination.

When the analysis was restricted only to cases of influenza that required hospitalization, a 39% reduction in risk was found for infants of women who had been vaccinated, compared with those of mothers who had not been vaccinated.

Cord blood samples or infant blood samples taken at 2–3 months of age were available for 160 study subjects. In this subgroup, the risk of influenza infection declined with increasing antibody titers.

The exact mechanism by which vaccination of the mother conferred protection to the infant is not certain. It may be due to maternal influenza antibodies being acquired transplacentally or through breastfeeding, or to reduced infant exposure to influenza in the mother. It even could be due to residual confounding not accounted for in the statistical analyses, but the finding of significantly higher antibody titers in 2- to 3-month-old infants who did not develop illness argues against that possibility, Dr. Eick and her colleagues said.

The study was funded by the U.S. Department of Health and Human Services' National Vaccine Program Office, the Office of Minority and Women's Health (now the Office of Health Disparities), the Centers for Disease Control and Prevention, Aventis-Pasteur, and Evans-Powderject. One of Dr. Eick's associates reported ties with MedImmune, Pfizer, and Sanofi-Pasteur, all of which manufacture influenza vaccine.

Vaccinating pregnant women against seasonal influenza reduced the risk of laboratory-confirmed influenza infection in their infants by 41%, according to a study.

Maternal immunization similarly cut by 39% the risk that infants up to 6 months of age would be hospitalized for influenza-like illness, said Angelia A. Eick, Ph.D., of the Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.

Influenza vaccination is already recommended for pregnant women to reduce their risk of developing flu-related complications. "These findings provide support for the added benefit of protecting infants from influenza virus infection up to 6 months, the period when infants are not eligible for influenza vaccination but are at highest risk of severe influenza illness," they noted.

Even though such immunization is recommended during pregnancy, it is not well accepted in the United States and many pregnant women do not get vaccinated. Since it would be unethical to perform a randomized, controlled study of maternal vaccination, Dr. Eick and her colleagues conducted a nonrandomized observational study to assess whether immunization during pregnancy conferred protection to infants.

The study subjects were 1,160 mother-infant pairs in which approximately half the mothers (573) had chosen to receive seasonal flu vaccine while pregnant and the other half (587) had declined the vaccine. All were enrolled after delivering healthy singleton infants at seven hospitals serving the Navajo and White Mountain Apache Indian reservations in the southwestern United States during three flu seasons between 2002 and 2005.

A total of 605 infants developed influenza-like illness during the flu season following delivery. "We found a 41% reduction in the risk of laboratory-confirmed influenza virus infection for infants of influenza-vaccinated mothers compared with infants of unvaccinated mothers," the researchers said (Arch. Pediatr. Adolesc. Med. 2010 [doi10.1001/archpediatrics.2010.192]).

The incidence of influenza-like illness was 6.7 per 1,000 person-days for infants of mothers who had been vaccinated, compared with 7.2 per 1,000 person-days for infants of mothers who had not.

Among the infants whose mothers were vaccinated, there was a 41% reduction in the risk of laboratory-confirmed influenza virus infection compared with those whose mothers declined vaccination.

When the analysis was restricted only to cases of influenza that required hospitalization, a 39% reduction in risk was found for infants of women who had been vaccinated, compared with those of mothers who had not been vaccinated.

Cord blood samples or infant blood samples taken at 2–3 months of age were available for 160 study subjects. In this subgroup, the risk of influenza infection declined with increasing antibody titers.

The exact mechanism by which vaccination of the mother conferred protection to the infant is not certain. It may be due to maternal influenza antibodies being acquired transplacentally or through breastfeeding, or to reduced infant exposure to influenza in the mother. It even could be due to residual confounding not accounted for in the statistical analyses, but the finding of significantly higher antibody titers in 2- to 3-month-old infants who did not develop illness argues against that possibility, Dr. Eick and her colleagues said.

The study was funded by the U.S. Department of Health and Human Services' National Vaccine Program Office, the Office of Minority and Women's Health (now the Office of Health Disparities), the Centers for Disease Control and Prevention, Aventis-Pasteur, and Evans-Powderject. One of Dr. Eick's associates reported ties with MedImmune, Pfizer, and Sanofi-Pasteur, all of which manufacture influenza vaccine.

Major Finding: On a scale of 1–36, the median score of symptom severity was 14 for 2009 H1N1 influenza, compared with 16 for the seasonal flu in 2008–2009, and 17 for the seasonal flu in 2007–2008.

Data Source: A single-center, prospective study of all patients who tested positive for H1N1 or seasonal influenza A out of a population of approximately 50,000 adults and children residing in Wisconsin.

Disclosures: The study was funded by a grant from the Centers for Disease Control and Prevention, Atlanta. No financial conflicts of interest were reported.

The severity of the illness caused by the 2009 H1N1 pandemic was no worse than that caused by seasonal influenza A in a Wisconsin population of 50,000 children and adults.

“Our results suggest that the clinical manifestations and risk of hospital admission are similar for the 2009 H1N1 and other seasonal influenza A strains among those presenting for medical care and documented to have influenza infection,” wrote Dr. Edward A. Belongia of the Marshfield (Wisc.) Clinic Research Foundation and his associates.

Previous studies have been unable to make direct comparisons of the spectrum of influenza illnesses because all the data on H1N1 have been surveillance data, particularly reports on hospital admissions and fatalities. “These reports have provided valuable descriptive information, but differing criteria for influenza testing by season and the lack of uniform standards for data collection and reporting limit comparisons with other influenza viruses,” the authors said.

By contrast, their study made comparisons using a defined population in which enrollment and laboratory methods were consistent across all subjects. They compared the characteristics of the illness caused by the pandemic with those of the illness caused by seasonal flu infection using both inpatient and outpatient medical records for all residents of 14 ZIP code areas surrounding Marshfield, who receive all their medical care at the clinic facilities.

All of the patients who presented for medical care with at least one flu symptom were tested for influenza using nasopharyngeal or nasal swabs. The study periods included 10 weeks during the 2007–2008 flu season, 12 weeks during the 2008–2009 season, and 27 weeks during the 2009 pandemic. There were 545 cases of 2009 H1N1 infection, 221 cases of seasonal H1N1 in 2008–2009, and 632 cases of H3N2 infection in 2007–2008.

Symptom severity scores were calculated for each patient based on self- or parental report of the severity of cough, fever, chills, fatigue, wheezing, nasal congestion, vomiting, headache, muscle ache, sore throat, ear pain, and nausea. Possible scores ranged from 1 for a single mild symptom to 36 for 12 severe symptoms.

Symptom severity scores were comparable for the three infections, with a median score of 14 for 2009 H1N1, 16 for the 2008–2009 seasonal flu, and 17 for 2007–2008 seasonal flu. The proportion of patients who received antiviral medications was similar in all three study groups.

The cumulative incidence of hospital admission within 30 days of onset per 1,000 residents was 0.25 for H1N1, 0.15 for seasonal flu in 2008–2009, and 0.50 for seasonal flu in 2007–2008, which are nonsignificant differences, the researchers wrote (JAMA 2010;304:1091–8).

They said other studies “have reported a higher-than-expected incidence of hospitalization and death associated with 2009 H1N1 infection, particularly in children. This finding may be due to the greatly elevated incidence of 2009 H1N1 influenza in a highly susceptible population of children and young adults rather than increased virulence of 2009 H1N1 relative to seasonal influenza A viruses.”

The investigators cautioned that their findings regarding the most serious outcomes, such as pneumonia, were limited because of the very low number of such outcomes in all the study groups.

Major Finding: On a scale of 1–36, the median score of symptom severity was 14 for 2009 H1N1 influenza, compared with 16 for the seasonal flu in 2008–2009, and 17 for the seasonal flu in 2007–2008.

Data Source: A single-center, prospective study of all patients who tested positive for H1N1 or seasonal influenza A out of a population of approximately 50,000 adults and children residing in Wisconsin.

Disclosures: The study was funded by a grant from the Centers for Disease Control and Prevention, Atlanta. No financial conflicts of interest were reported.

The severity of the illness caused by the 2009 H1N1 pandemic was no worse than that caused by seasonal influenza A in a Wisconsin population of 50,000 children and adults.

“Our results suggest that the clinical manifestations and risk of hospital admission are similar for the 2009 H1N1 and other seasonal influenza A strains among those presenting for medical care and documented to have influenza infection,” wrote Dr. Edward A. Belongia of the Marshfield (Wisc.) Clinic Research Foundation and his associates.

Previous studies have been unable to make direct comparisons of the spectrum of influenza illnesses because all the data on H1N1 have been surveillance data, particularly reports on hospital admissions and fatalities. “These reports have provided valuable descriptive information, but differing criteria for influenza testing by season and the lack of uniform standards for data collection and reporting limit comparisons with other influenza viruses,” the authors said.

By contrast, their study made comparisons using a defined population in which enrollment and laboratory methods were consistent across all subjects. They compared the characteristics of the illness caused by the pandemic with those of the illness caused by seasonal flu infection using both inpatient and outpatient medical records for all residents of 14 ZIP code areas surrounding Marshfield, who receive all their medical care at the clinic facilities.

All of the patients who presented for medical care with at least one flu symptom were tested for influenza using nasopharyngeal or nasal swabs. The study periods included 10 weeks during the 2007–2008 flu season, 12 weeks during the 2008–2009 season, and 27 weeks during the 2009 pandemic. There were 545 cases of 2009 H1N1 infection, 221 cases of seasonal H1N1 in 2008–2009, and 632 cases of H3N2 infection in 2007–2008.

Symptom severity scores were calculated for each patient based on self- or parental report of the severity of cough, fever, chills, fatigue, wheezing, nasal congestion, vomiting, headache, muscle ache, sore throat, ear pain, and nausea. Possible scores ranged from 1 for a single mild symptom to 36 for 12 severe symptoms.

Symptom severity scores were comparable for the three infections, with a median score of 14 for 2009 H1N1, 16 for the 2008–2009 seasonal flu, and 17 for 2007–2008 seasonal flu. The proportion of patients who received antiviral medications was similar in all three study groups.

The cumulative incidence of hospital admission within 30 days of onset per 1,000 residents was 0.25 for H1N1, 0.15 for seasonal flu in 2008–2009, and 0.50 for seasonal flu in 2007–2008, which are nonsignificant differences, the researchers wrote (JAMA 2010;304:1091–8).

They said other studies “have reported a higher-than-expected incidence of hospitalization and death associated with 2009 H1N1 infection, particularly in children. This finding may be due to the greatly elevated incidence of 2009 H1N1 influenza in a highly susceptible population of children and young adults rather than increased virulence of 2009 H1N1 relative to seasonal influenza A viruses.”

The investigators cautioned that their findings regarding the most serious outcomes, such as pneumonia, were limited because of the very low number of such outcomes in all the study groups.

Major Finding: On a scale of 1–36, the median score of symptom severity was 14 for 2009 H1N1 influenza, compared with 16 for the seasonal flu in 2008–2009, and 17 for the seasonal flu in 2007–2008.

Data Source: A single-center, prospective study of all patients who tested positive for H1N1 or seasonal influenza A out of a population of approximately 50,000 adults and children residing in Wisconsin.

Disclosures: The study was funded by a grant from the Centers for Disease Control and Prevention, Atlanta. No financial conflicts of interest were reported.

The severity of the illness caused by the 2009 H1N1 pandemic was no worse than that caused by seasonal influenza A in a Wisconsin population of 50,000 children and adults.

“Our results suggest that the clinical manifestations and risk of hospital admission are similar for the 2009 H1N1 and other seasonal influenza A strains among those presenting for medical care and documented to have influenza infection,” wrote Dr. Edward A. Belongia of the Marshfield (Wisc.) Clinic Research Foundation and his associates.

Previous studies have been unable to make direct comparisons of the spectrum of influenza illnesses because all the data on H1N1 have been surveillance data, particularly reports on hospital admissions and fatalities. “These reports have provided valuable descriptive information, but differing criteria for influenza testing by season and the lack of uniform standards for data collection and reporting limit comparisons with other influenza viruses,” the authors said.

By contrast, their study made comparisons using a defined population in which enrollment and laboratory methods were consistent across all subjects. They compared the characteristics of the illness caused by the pandemic with those of the illness caused by seasonal flu infection using both inpatient and outpatient medical records for all residents of 14 ZIP code areas surrounding Marshfield, who receive all their medical care at the clinic facilities.

All of the patients who presented for medical care with at least one flu symptom were tested for influenza using nasopharyngeal or nasal swabs. The study periods included 10 weeks during the 2007–2008 flu season, 12 weeks during the 2008–2009 season, and 27 weeks during the 2009 pandemic. There were 545 cases of 2009 H1N1 infection, 221 cases of seasonal H1N1 in 2008–2009, and 632 cases of H3N2 infection in 2007–2008.

Symptom severity scores were calculated for each patient based on self- or parental report of the severity of cough, fever, chills, fatigue, wheezing, nasal congestion, vomiting, headache, muscle ache, sore throat, ear pain, and nausea. Possible scores ranged from 1 for a single mild symptom to 36 for 12 severe symptoms.

Symptom severity scores were comparable for the three infections, with a median score of 14 for 2009 H1N1, 16 for the 2008–2009 seasonal flu, and 17 for 2007–2008 seasonal flu. The proportion of patients who received antiviral medications was similar in all three study groups.

The cumulative incidence of hospital admission within 30 days of onset per 1,000 residents was 0.25 for H1N1, 0.15 for seasonal flu in 2008–2009, and 0.50 for seasonal flu in 2007–2008, which are nonsignificant differences, the researchers wrote (JAMA 2010;304:1091–8).

They said other studies “have reported a higher-than-expected incidence of hospitalization and death associated with 2009 H1N1 infection, particularly in children. This finding may be due to the greatly elevated incidence of 2009 H1N1 influenza in a highly susceptible population of children and young adults rather than increased virulence of 2009 H1N1 relative to seasonal influenza A viruses.”

The investigators cautioned that their findings regarding the most serious outcomes, such as pneumonia, were limited because of the very low number of such outcomes in all the study groups.

Major Finding: Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV7) immunization in several countries. However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV7 vaccine.“W

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV7 in nasopharyngeal acquisition of serotype 19A. In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. Elske J.M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

They performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV7 vaccines were first introduced. The 948 study subjects had been randomly assigned to receive PCV7 at ages 2 and 4 months (the 2-dose group), or PCV7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV7 (the unvaccinated control group). Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, the investigators said (JAMA 2010;304:1099–106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group. This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, they noted. One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand.”

Major Finding: Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV7) immunization in several countries. However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV7 vaccine.“W

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV7 in nasopharyngeal acquisition of serotype 19A. In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. Elske J.M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

They performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV7 vaccines were first introduced. The 948 study subjects had been randomly assigned to receive PCV7 at ages 2 and 4 months (the 2-dose group), or PCV7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV7 (the unvaccinated control group). Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, the investigators said (JAMA 2010;304:1099–106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group. This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, they noted. One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand.”

Major Finding: Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV7) immunization in several countries. However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV7 vaccine.“W

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV7 in nasopharyngeal acquisition of serotype 19A. In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. Elske J.M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

They performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV7 vaccines were first introduced. The 948 study subjects had been randomly assigned to receive PCV7 at ages 2 and 4 months (the 2-dose group), or PCV7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV7 (the unvaccinated control group). Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, the investigators said (JAMA 2010;304:1099–106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group. This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, they noted. One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand.”

Pediatric asthma hospitalizations decreased by about 20% per year after a ban on smoking in enclosed public spaces was enacted in Scotland, said Daniel Mackay, Ph.D., of the University of Glasgow and his associates.

Before the legislation was implemented, there was concern that people might transfer their smoking from public areas to their homes, “leading paradoxically to an increase in exposure … among children,” they said (N. Engl. J. Med. 2010;363:1139–45).

Such displacement of smoking activity has not occurred. Instead, the results support the conclusion of another study that found that the public ban on smoking was followed by an increase in voluntary smoking restrictions in homes as well, the investigators said.

They used government databases to identify all 21,415 asthma admissions across Scotland from January 2000 through October 2009 for children younger than 15 years.

In the period from 2000 until implementation of the smoking ban in 2006, hospital admissions for asthma rose an adjusted average of 4.4% per year.

In the period after the smoking ban was enacted, the risk-adjusted annual rate of pediatric asthma admissions declined 19.5%, a statistically significant difference. The rate of asthma hospitalizations decreased both in preschool and school-age children, Dr. Mackay and his colleagues said.

NHS Health Scotland funded the study. The investigators had no relevant conflicts of interest.

Pediatric asthma hospitalizations decreased by about 20% per year after a ban on smoking in enclosed public spaces was enacted in Scotland, said Daniel Mackay, Ph.D., of the University of Glasgow and his associates.

Before the legislation was implemented, there was concern that people might transfer their smoking from public areas to their homes, “leading paradoxically to an increase in exposure … among children,” they said (N. Engl. J. Med. 2010;363:1139–45).

Such displacement of smoking activity has not occurred. Instead, the results support the conclusion of another study that found that the public ban on smoking was followed by an increase in voluntary smoking restrictions in homes as well, the investigators said.

They used government databases to identify all 21,415 asthma admissions across Scotland from January 2000 through October 2009 for children younger than 15 years.

In the period from 2000 until implementation of the smoking ban in 2006, hospital admissions for asthma rose an adjusted average of 4.4% per year.

In the period after the smoking ban was enacted, the risk-adjusted annual rate of pediatric asthma admissions declined 19.5%, a statistically significant difference. The rate of asthma hospitalizations decreased both in preschool and school-age children, Dr. Mackay and his colleagues said.

NHS Health Scotland funded the study. The investigators had no relevant conflicts of interest.

Pediatric asthma hospitalizations decreased by about 20% per year after a ban on smoking in enclosed public spaces was enacted in Scotland, said Daniel Mackay, Ph.D., of the University of Glasgow and his associates.

Before the legislation was implemented, there was concern that people might transfer their smoking from public areas to their homes, “leading paradoxically to an increase in exposure … among children,” they said (N. Engl. J. Med. 2010;363:1139–45).

Such displacement of smoking activity has not occurred. Instead, the results support the conclusion of another study that found that the public ban on smoking was followed by an increase in voluntary smoking restrictions in homes as well, the investigators said.

They used government databases to identify all 21,415 asthma admissions across Scotland from January 2000 through October 2009 for children younger than 15 years.

In the period from 2000 until implementation of the smoking ban in 2006, hospital admissions for asthma rose an adjusted average of 4.4% per year.

In the period after the smoking ban was enacted, the risk-adjusted annual rate of pediatric asthma admissions declined 19.5%, a statistically significant difference. The rate of asthma hospitalizations decreased both in preschool and school-age children, Dr. Mackay and his colleagues said.

NHS Health Scotland funded the study. The investigators had no relevant conflicts of interest.

Major Finding: A COPD patient's frequency of exacerbations remains stable over time, and the subgroup of patients with frequent exacerbations appears to have a particular phenotype of the disease.

Data Source: A secondary analysis of data collected in the multinational, prospective, observational, 3-year ECLIPSE study of 2,138 patients with mild, moderate, or severe COPD.

Disclosures: The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study — the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) — to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40–75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV₁) of less than 80% of predicted value, and an FEV₁-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128–38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations in the third year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient's susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

View on the News

What Is the Mechanism?

The finding of a distinct phenotype of chronic obstructive pulmonary disease implies that some underlying genetic, biologic, or behavioral mechanism determines either susceptibility or resistance to recurrent exacerbations, independent of disease severity, according to Dr. Donald P. Tashkin.

“Such a mechanism could include greater or lesser susceptibility to respiratory tract infection (the principal trigger of exacerbations); microaspiration from gastroesophageal reflux; psychological factors such as perception of dyspnea (the major symptom of exacerbation); and medication adherence.

“Understanding the mechanistic basis for frequent exacerbations might lead to more effective preventive therapy,” he wrote.

It is important for clinicians to identify which patients fit the phenotype, because effective therapies are already available to curb the frequency of exacerbations.

In addition, “a better understanding of the underlying mechanisms that predispose a patient to exacerbations could lead to the development of more targeted preventive strategies,” which in turn would favorably affect the overall course of COPD, he added.

Major Finding: A COPD patient's frequency of exacerbations remains stable over time, and the subgroup of patients with frequent exacerbations appears to have a particular phenotype of the disease.

Data Source: A secondary analysis of data collected in the multinational, prospective, observational, 3-year ECLIPSE study of 2,138 patients with mild, moderate, or severe COPD.

Disclosures: The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study — the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) — to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40–75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV₁) of less than 80% of predicted value, and an FEV₁-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128–38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations in the third year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient's susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

View on the News

What Is the Mechanism?

The finding of a distinct phenotype of chronic obstructive pulmonary disease implies that some underlying genetic, biologic, or behavioral mechanism determines either susceptibility or resistance to recurrent exacerbations, independent of disease severity, according to Dr. Donald P. Tashkin.

“Such a mechanism could include greater or lesser susceptibility to respiratory tract infection (the principal trigger of exacerbations); microaspiration from gastroesophageal reflux; psychological factors such as perception of dyspnea (the major symptom of exacerbation); and medication adherence.

“Understanding the mechanistic basis for frequent exacerbations might lead to more effective preventive therapy,” he wrote.

It is important for clinicians to identify which patients fit the phenotype, because effective therapies are already available to curb the frequency of exacerbations.

In addition, “a better understanding of the underlying mechanisms that predispose a patient to exacerbations could lead to the development of more targeted preventive strategies,” which in turn would favorably affect the overall course of COPD, he added.

Major Finding: A COPD patient's frequency of exacerbations remains stable over time, and the subgroup of patients with frequent exacerbations appears to have a particular phenotype of the disease.

Data Source: A secondary analysis of data collected in the multinational, prospective, observational, 3-year ECLIPSE study of 2,138 patients with mild, moderate, or severe COPD.

Disclosures: The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study — the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) — to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40–75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV₁) of less than 80% of predicted value, and an FEV₁-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128–38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations in the third year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient's susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

View on the News

What Is the Mechanism?

The finding of a distinct phenotype of chronic obstructive pulmonary disease implies that some underlying genetic, biologic, or behavioral mechanism determines either susceptibility or resistance to recurrent exacerbations, independent of disease severity, according to Dr. Donald P. Tashkin.

“Such a mechanism could include greater or lesser susceptibility to respiratory tract infection (the principal trigger of exacerbations); microaspiration from gastroesophageal reflux; psychological factors such as perception of dyspnea (the major symptom of exacerbation); and medication adherence.

“Understanding the mechanistic basis for frequent exacerbations might lead to more effective preventive therapy,” he wrote.

It is important for clinicians to identify which patients fit the phenotype, because effective therapies are already available to curb the frequency of exacerbations.

In addition, “a better understanding of the underlying mechanisms that predispose a patient to exacerbations could lead to the development of more targeted preventive strategies,” which in turn would favorably affect the overall course of COPD, he added.

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology.

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society's epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50–74 years at baseline in 1992–1993 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11–15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said. They also suggest that the use of insulin probably doesn't raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A_1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology.

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society's epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50–74 years at baseline in 1992–1993 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11–15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said. They also suggest that the use of insulin probably doesn't raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A_1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.

Men with type 2 diabetes have a moderately higher risk of developing colorectal cancer than do men who are not diabetic, Peter T. Campbell, Ph.D., and his colleagues said in the October issue of Gastroenterology.

In contrast, type 2 diabetes shows no association with colorectal cancer risk among women. The reason for this gender discrepancy is unknown, said Dr. Campbell of the American Cancer Society's epidemiology research program, and his coauthors.

Nevertheless, “these results emphasize the need for diligent adherence to recommended guidelines for colorectal cancer early detection among men with longstanding type 2 diabetes,” they noted.

A 2005 meta-analysis of epidemiologic studies found that type 2 diabetes moderately raised the risk of colorectal cancer in both sexes, but more recent analyses have consistently demonstrated a stronger association for men than for women. Given the high worldwide prevalence of diabetes and the significant morbidity and mortality associated with colorectal cancer, any link between the two diseases would have strong public health and clinical relevance, the investigators said.

They studied the relationship between diabetes and colorectal cancer using data from the Cancer Prevention Study II Nutrition Cohort. Participants were aged 50–74 years at baseline in 1992–1993 and were followed through 2007.

In a sample of 73,312 men and 81,663 women from this cohort, 1,567 men and 1,242 women developed incident colon or rectal cancer. A total of 227 of these men and 108 of the women reported they had type 2 diabetes.

For men, diabetes was associated with a 24% higher risk of colorectal cancer. The link did not differ meaningfully by tumor stage or location within the colorectum. The risk was not markedly different between men who reported using insulin and those who did not.

The cancer risk increased with duration of diabetes. There was a null association with diabetes of up to 10 years duration, a relative risk of 1.35 for diabetes of 11–15 years duration, and a relative risk of 1.73 for diabetes of more than 15 years duration.

In contrast, among women there was no association between diabetes and colorectal cancer.

“These findings provide at least partial support for the hypothesis that hyperinsulinemia, hyperglycemia, or related cofactors are associated with higher colorectal cancer risk,” Dr. Campbell and his colleagues said. They also suggest that the use of insulin probably doesn't raise the risk of colorectal cancer substantially, the researchers added.

The reason for the difference in risk between men and women is not known, but it may be related to their differences in the degree of glucose control in recent years. National data suggest that women have better hemoglobin A_1c levels than do men and are more apt to take metformin, both of which suggest that women have better glucose control.

The researchers also found a stronger association between diabetes and colorectal cancer among patients who reported a family history of colorectal cancer (RR 1.91) than among diabetics who had no family history of the cancer (RR 1.12). “To our knowledge, these are the first data to suggest that family history of colorectal cancer may modify the association between type 2 diabetes and colorectal cancer,” the team said.

This study was limited by its reliance on patient self-reports and the lack of pharmacologic data on diabetes therapy or degree of glucose control.

This study was supported by the American Cancer Society. No conflicts of interest were reported by the authors.