Mary Ann Moon

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen's University Belfast (Ireland), and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” the investigators noted.

They searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world's largest computerized database of anonymized longitudinal patient records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

The investigators reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice.

During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined.

This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H₂ receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion … we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

Access to the GPRD database was funded by the Medical Research Council.

Dr. Cardwell reported no financial conflicts of interest.

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen's University Belfast (Ireland), and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” the investigators noted.

They searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world's largest computerized database of anonymized longitudinal patient records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

The investigators reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice.

During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined.

This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H₂ receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion … we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

Access to the GPRD database was funded by the Medical Research Council.

Dr. Cardwell reported no financial conflicts of interest.

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen's University Belfast (Ireland), and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” the investigators noted.

They searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world's largest computerized database of anonymized longitudinal patient records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

The investigators reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice.

During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined.

This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H₂ receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion … we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

Access to the GPRD database was funded by the Medical Research Council.

Dr. Cardwell reported no financial conflicts of interest.

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 accompanying the new guideline.

The review by the expert panel 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 a period of 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, according to Dr. Burstein and his colleagues (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756

Among the committee's 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 a period of 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 unknown. 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 aromatase inhibitors (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 by patients. 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 cardiovascular toxicity.

AIs also frequently 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 their 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 with AI therapy. In one study of patients taking tamoxifen, 60% of those 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 online 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 accompanying the new guideline.

The review by the expert panel 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 a period of 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, according to Dr. Burstein and his colleagues (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756

Among the committee's 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 a period of 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 unknown. 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 aromatase inhibitors (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 by patients. 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 cardiovascular toxicity.

AIs also frequently 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 their 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 with AI therapy. In one study of patients taking tamoxifen, 60% of those 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 online 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 accompanying the new guideline.

The review by the expert panel 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 a period of 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, according to Dr. Burstein and his colleagues (J. Clin. Oncol. 2010 [doi:10.1200/JCO.2009.26.3756

Among the committee's 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 a period of 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 unknown. 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 aromatase inhibitors (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 by patients. 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 cardiovascular toxicity.

AIs also frequently 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 their 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 with AI therapy. In one study of patients taking tamoxifen, 60% of those 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 online at www.asco.org/guidelines/endocrinebreastwww.cancer.net

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

Major Finding: Target-lesion failure at 1 year occurred in 8.2% of zotarolimus-eluting stent patients and 8.3% of everolimus-eluting stent patients; 1-year mortality from any cause was 1.6% (zotarolimus group) vs. 2.8% (everolimus group), nonsignificant differences. Significant differences in in-hospital and 30-day mortality favored the zotarolimus stent. The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

Data Source: Multicenter open-label, randomized study comparing zotarolimus-eluting stents (1,140 patients with 1,661 lesions) with everolimus-eluting stents (1,152 patients with 1,705 lesions).

Disclosures: Dr. Serruys and some associates reported ties to Medtronic Inc., Boston Scientific Corp., and Abbott Labs, maker of the everolimus-eluting stent. The study was sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent.

One year after implantation, the zotarolimus-eluting coronary stent was found to be noninferior to the everolimus-eluting stent in preventing target-lesion failure.

This “new-generation” stent was tested in a large population with a mix of traits usually excluded from randomized clinical trials of stents, including multivessel intervention, small-vessel disease, long lesions, bifurcations, or trifurcations. “Therefore, we consider that our findings are highly generalizable to patients in everyday clinical practice,” said Dr. Patrick W. Serruys of Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

In the multicenter open-label study, sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent, patients were randomly assigned to undergo percutaneous coronary intervention (PCI) with placement of either zotarolimus-eluting (1,140 patients with 1,661 lesions) or everolimus-eluting stents (1,152 patients with 1,705 lesions). Patients were followed by telephone or hospital visit at 1, 6, and 12 months, and will be followed annually for 5 years.

The primary end point was target-lesion failure at 1 year, defined as a composite of death from cardiac causes, MI, or target-lesion revascularization. This occurred in 8.2% of patients who received zotarolimus-eluting stents and 8.3% of those who received everolimus-eluting stents, a nonsignificant difference.

The zotarolimus-stent group had significantly reduced rates of death from any cause while they were hospitalized (0.1% vs. 0.8%) and at 30 days (0.2% vs. 0.9%), compared with the everolimus-stent group. However, the 1-year mortality from any cause was 1.6% in the zotarolimus group and 2.8% in the everolimus group, a nonsignificant difference, the investigators said (N. Engl. J. Med. 2010 [10.1056/NEJMoa1004130]).

These results remained consistent across all subgroups of patients. At least one off-label criterion was present in the majority (66.3%) of the patients.

The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

A smaller percentage of patients than expected underwent angiographic assessment of in-stent stenosis. In-stent stenosis was worse in the zotarolimus group but still met the criterion for noninferiority, Dr. Serruys and his colleagues said.

The rates of adverse events were low and compared favorably with those in previous studies, with no significant between-group differences, they added.

“Although our findings are hypothesis generating and require additional investigation, definitive conclusions will be obtained only from longer-term follow-up in large patient populations in studies that have sufficient statistical power to detect differences in rates of stent thrombosis,” the researchers said.

Major Finding: Target-lesion failure at 1 year occurred in 8.2% of zotarolimus-eluting stent patients and 8.3% of everolimus-eluting stent patients; 1-year mortality from any cause was 1.6% (zotarolimus group) vs. 2.8% (everolimus group), nonsignificant differences. Significant differences in in-hospital and 30-day mortality favored the zotarolimus stent. The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

Data Source: Multicenter open-label, randomized study comparing zotarolimus-eluting stents (1,140 patients with 1,661 lesions) with everolimus-eluting stents (1,152 patients with 1,705 lesions).

Disclosures: Dr. Serruys and some associates reported ties to Medtronic Inc., Boston Scientific Corp., and Abbott Labs, maker of the everolimus-eluting stent. The study was sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent.

One year after implantation, the zotarolimus-eluting coronary stent was found to be noninferior to the everolimus-eluting stent in preventing target-lesion failure.

This “new-generation” stent was tested in a large population with a mix of traits usually excluded from randomized clinical trials of stents, including multivessel intervention, small-vessel disease, long lesions, bifurcations, or trifurcations. “Therefore, we consider that our findings are highly generalizable to patients in everyday clinical practice,” said Dr. Patrick W. Serruys of Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

In the multicenter open-label study, sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent, patients were randomly assigned to undergo percutaneous coronary intervention (PCI) with placement of either zotarolimus-eluting (1,140 patients with 1,661 lesions) or everolimus-eluting stents (1,152 patients with 1,705 lesions). Patients were followed by telephone or hospital visit at 1, 6, and 12 months, and will be followed annually for 5 years.

The primary end point was target-lesion failure at 1 year, defined as a composite of death from cardiac causes, MI, or target-lesion revascularization. This occurred in 8.2% of patients who received zotarolimus-eluting stents and 8.3% of those who received everolimus-eluting stents, a nonsignificant difference.

The zotarolimus-stent group had significantly reduced rates of death from any cause while they were hospitalized (0.1% vs. 0.8%) and at 30 days (0.2% vs. 0.9%), compared with the everolimus-stent group. However, the 1-year mortality from any cause was 1.6% in the zotarolimus group and 2.8% in the everolimus group, a nonsignificant difference, the investigators said (N. Engl. J. Med. 2010 [10.1056/NEJMoa1004130]).

These results remained consistent across all subgroups of patients. At least one off-label criterion was present in the majority (66.3%) of the patients.

The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

A smaller percentage of patients than expected underwent angiographic assessment of in-stent stenosis. In-stent stenosis was worse in the zotarolimus group but still met the criterion for noninferiority, Dr. Serruys and his colleagues said.

The rates of adverse events were low and compared favorably with those in previous studies, with no significant between-group differences, they added.

“Although our findings are hypothesis generating and require additional investigation, definitive conclusions will be obtained only from longer-term follow-up in large patient populations in studies that have sufficient statistical power to detect differences in rates of stent thrombosis,” the researchers said.

Major Finding: Target-lesion failure at 1 year occurred in 8.2% of zotarolimus-eluting stent patients and 8.3% of everolimus-eluting stent patients; 1-year mortality from any cause was 1.6% (zotarolimus group) vs. 2.8% (everolimus group), nonsignificant differences. Significant differences in in-hospital and 30-day mortality favored the zotarolimus stent. The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

Data Source: Multicenter open-label, randomized study comparing zotarolimus-eluting stents (1,140 patients with 1,661 lesions) with everolimus-eluting stents (1,152 patients with 1,705 lesions).

Disclosures: Dr. Serruys and some associates reported ties to Medtronic Inc., Boston Scientific Corp., and Abbott Labs, maker of the everolimus-eluting stent. The study was sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent.

One year after implantation, the zotarolimus-eluting coronary stent was found to be noninferior to the everolimus-eluting stent in preventing target-lesion failure.

This “new-generation” stent was tested in a large population with a mix of traits usually excluded from randomized clinical trials of stents, including multivessel intervention, small-vessel disease, long lesions, bifurcations, or trifurcations. “Therefore, we consider that our findings are highly generalizable to patients in everyday clinical practice,” said Dr. Patrick W. Serruys of Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

In the multicenter open-label study, sponsored by Medtronic CardioVascular, maker of the zotarolimus-eluting stent, patients were randomly assigned to undergo percutaneous coronary intervention (PCI) with placement of either zotarolimus-eluting (1,140 patients with 1,661 lesions) or everolimus-eluting stents (1,152 patients with 1,705 lesions). Patients were followed by telephone or hospital visit at 1, 6, and 12 months, and will be followed annually for 5 years.

The primary end point was target-lesion failure at 1 year, defined as a composite of death from cardiac causes, MI, or target-lesion revascularization. This occurred in 8.2% of patients who received zotarolimus-eluting stents and 8.3% of those who received everolimus-eluting stents, a nonsignificant difference.

The zotarolimus-stent group had significantly reduced rates of death from any cause while they were hospitalized (0.1% vs. 0.8%) and at 30 days (0.2% vs. 0.9%), compared with the everolimus-stent group. However, the 1-year mortality from any cause was 1.6% in the zotarolimus group and 2.8% in the everolimus group, a nonsignificant difference, the investigators said (N. Engl. J. Med. 2010 [10.1056/NEJMoa1004130]).

These results remained consistent across all subgroups of patients. At least one off-label criterion was present in the majority (66.3%) of the patients.

The rate of definite stent thrombosis was significantly higher in the zotarolimus group (1.2%) than the everolimus group (0.3%).

A smaller percentage of patients than expected underwent angiographic assessment of in-stent stenosis. In-stent stenosis was worse in the zotarolimus group but still met the criterion for noninferiority, Dr. Serruys and his colleagues said.

The rates of adverse events were low and compared favorably with those in previous studies, with no significant between-group differences, they added.

“Although our findings are hypothesis generating and require additional investigation, definitive conclusions will be obtained only from longer-term follow-up in large patient populations in studies that have sufficient statistical power to detect differences in rates of stent thrombosis,” the researchers said.

Transporting emergency services' patients with ST-segment myocardial infarction only to those hospitals that already have percutaneous coronary intervention capability increases access to the procedure and is much more cost effective than constructing new or expanding existing PCI centers and staffing them, according to a computer-simulated study.

“Our results strongly suggest that construction and staffing of new PCI [facilities] may not be warranted if an [emergency medical service] strategy is both available and feasible,” wrote Thomas W. Concannon, Ph.D., of the Center for Cardiovascular Health Services Research, Tufts Medical Center, Boston, and his associates.

The researchers used mathematical modeling to compare the benefits and costs of various approaches for improving patient access to PCI. “We simulated EMS transport, reperfusion strategy, clinical outcomes, and costs for 2,000 patients, representing approximately 1 year of STEMIs in a municipal area the size of Dallas County, Texas.” This region comprises an ethnically diverse population in urban, suburban, and rural areas.

The models incorporated predicted rates of post-MI stroke, congestive heart failure, reinfarction, and mortality at 30 days and 6 months.

The investigators compared outcomes between a strategy in which EMS providers transported patients only to existing PCI-capable hospitals and another in which EMS providers transported patients to the nearest hospital, regardless of PCI capability. They assessed 13 scenarios in which either hospital PCI capability was constructed from scratch or existing PCI services were expanded incrementally (for example, from part-time to full-time operating hours, from basic to fuller staff coverage, and from providing no backup coronary artery bypass surgery suite to providing an on-site CABG suite).

All models increased patient access to PCI. However, the strategy in which patients were taken only to hospitals with PCI capability was by far the best, allowing 1,391 of the 2,000 patients to receive PCI, the investigators wrote (Circ. Cardiovasc. Qual. Outcomes 2010 [doi:10.1161/CIRCOUTCOMES.109.908541]).

This strategy also was the most cost effective, with a cost per quality-adjusted life-year (QALY) saved of $506.

In comparison, the most cost-effective of the 13 hospital-based scenarios—to expand existing part-time PCI centers within the two highest-volume hospitals so that they had on-call staff covering nights and weekends—allowed only 913 of the 2,000 patients to receive PCI, at a cost per QALY saved of $10,000.

The remaining scenarios increased the number of patients who received PCI to varying degrees, but did so at much higher costs of up to $85,000 per QALY saved.

None of these models explored an approach in which the STEMI patients were stratified so that only those most likely to benefit from PCI would be diverted to PCI-capable hospitals. “We believe an even stronger case could be made for a strategy that involves selective transport of only those patients who are individually predicted to benefit,” Dr. Concannon and his associates said.

“Our results suggest that regional planners should consider EMS strategies for increasing access to PCI before adopting strategies involving new construction or increased staffing of PCI hospitals,” they said.

This study was supported by the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and a Tufts Medical Center-Pfizer career development award. No conflicts of interest were reported.

Transporting emergency services' patients with ST-segment myocardial infarction only to those hospitals that already have percutaneous coronary intervention capability increases access to the procedure and is much more cost effective than constructing new or expanding existing PCI centers and staffing them, according to a computer-simulated study.

“Our results strongly suggest that construction and staffing of new PCI [facilities] may not be warranted if an [emergency medical service] strategy is both available and feasible,” wrote Thomas W. Concannon, Ph.D., of the Center for Cardiovascular Health Services Research, Tufts Medical Center, Boston, and his associates.

The researchers used mathematical modeling to compare the benefits and costs of various approaches for improving patient access to PCI. “We simulated EMS transport, reperfusion strategy, clinical outcomes, and costs for 2,000 patients, representing approximately 1 year of STEMIs in a municipal area the size of Dallas County, Texas.” This region comprises an ethnically diverse population in urban, suburban, and rural areas.

The models incorporated predicted rates of post-MI stroke, congestive heart failure, reinfarction, and mortality at 30 days and 6 months.

The investigators compared outcomes between a strategy in which EMS providers transported patients only to existing PCI-capable hospitals and another in which EMS providers transported patients to the nearest hospital, regardless of PCI capability. They assessed 13 scenarios in which either hospital PCI capability was constructed from scratch or existing PCI services were expanded incrementally (for example, from part-time to full-time operating hours, from basic to fuller staff coverage, and from providing no backup coronary artery bypass surgery suite to providing an on-site CABG suite).

All models increased patient access to PCI. However, the strategy in which patients were taken only to hospitals with PCI capability was by far the best, allowing 1,391 of the 2,000 patients to receive PCI, the investigators wrote (Circ. Cardiovasc. Qual. Outcomes 2010 [doi:10.1161/CIRCOUTCOMES.109.908541]).

This strategy also was the most cost effective, with a cost per quality-adjusted life-year (QALY) saved of $506.

In comparison, the most cost-effective of the 13 hospital-based scenarios—to expand existing part-time PCI centers within the two highest-volume hospitals so that they had on-call staff covering nights and weekends—allowed only 913 of the 2,000 patients to receive PCI, at a cost per QALY saved of $10,000.

The remaining scenarios increased the number of patients who received PCI to varying degrees, but did so at much higher costs of up to $85,000 per QALY saved.

None of these models explored an approach in which the STEMI patients were stratified so that only those most likely to benefit from PCI would be diverted to PCI-capable hospitals. “We believe an even stronger case could be made for a strategy that involves selective transport of only those patients who are individually predicted to benefit,” Dr. Concannon and his associates said.

“Our results suggest that regional planners should consider EMS strategies for increasing access to PCI before adopting strategies involving new construction or increased staffing of PCI hospitals,” they said.

This study was supported by the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and a Tufts Medical Center-Pfizer career development award. No conflicts of interest were reported.

Transporting emergency services' patients with ST-segment myocardial infarction only to those hospitals that already have percutaneous coronary intervention capability increases access to the procedure and is much more cost effective than constructing new or expanding existing PCI centers and staffing them, according to a computer-simulated study.

“Our results strongly suggest that construction and staffing of new PCI [facilities] may not be warranted if an [emergency medical service] strategy is both available and feasible,” wrote Thomas W. Concannon, Ph.D., of the Center for Cardiovascular Health Services Research, Tufts Medical Center, Boston, and his associates.

The researchers used mathematical modeling to compare the benefits and costs of various approaches for improving patient access to PCI. “We simulated EMS transport, reperfusion strategy, clinical outcomes, and costs for 2,000 patients, representing approximately 1 year of STEMIs in a municipal area the size of Dallas County, Texas.” This region comprises an ethnically diverse population in urban, suburban, and rural areas.

The models incorporated predicted rates of post-MI stroke, congestive heart failure, reinfarction, and mortality at 30 days and 6 months.

The investigators compared outcomes between a strategy in which EMS providers transported patients only to existing PCI-capable hospitals and another in which EMS providers transported patients to the nearest hospital, regardless of PCI capability. They assessed 13 scenarios in which either hospital PCI capability was constructed from scratch or existing PCI services were expanded incrementally (for example, from part-time to full-time operating hours, from basic to fuller staff coverage, and from providing no backup coronary artery bypass surgery suite to providing an on-site CABG suite).

All models increased patient access to PCI. However, the strategy in which patients were taken only to hospitals with PCI capability was by far the best, allowing 1,391 of the 2,000 patients to receive PCI, the investigators wrote (Circ. Cardiovasc. Qual. Outcomes 2010 [doi:10.1161/CIRCOUTCOMES.109.908541]).

This strategy also was the most cost effective, with a cost per quality-adjusted life-year (QALY) saved of $506.

In comparison, the most cost-effective of the 13 hospital-based scenarios—to expand existing part-time PCI centers within the two highest-volume hospitals so that they had on-call staff covering nights and weekends—allowed only 913 of the 2,000 patients to receive PCI, at a cost per QALY saved of $10,000.

The remaining scenarios increased the number of patients who received PCI to varying degrees, but did so at much higher costs of up to $85,000 per QALY saved.

None of these models explored an approach in which the STEMI patients were stratified so that only those most likely to benefit from PCI would be diverted to PCI-capable hospitals. “We believe an even stronger case could be made for a strategy that involves selective transport of only those patients who are individually predicted to benefit,” Dr. Concannon and his associates said.

“Our results suggest that regional planners should consider EMS strategies for increasing access to PCI before adopting strategies involving new construction or increased staffing of PCI hospitals,” they said.

This study was supported by the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and a Tufts Medical Center-Pfizer career development award. No conflicts of interest were reported.

Greater waist circumference was associated with a higher mortality risk independent of body mass index, according to a recent report.

Waist circumference is positively associated with mortality risk within all categories of BMI—normal, overweight, and obese. In fact, the relationship between greater waist circumference and higher mortality is strongest among women with a normal BMI, said Eric J. Jacobs, Ph.D., and his associates, who are with the epidemiology research program at the American Cancer Society in Atlanta.

The link between waist circumference and mortality has been reported in numerous studies, but this is the first study to examine that association within the standard categories of BMI, they noted (Arch. Intern. Med. 2010;170:1293-1301).

Dr. Jacobs and his colleagues used data from the Cancer Prevention Study II Nutrition Cohort, a large prospective study that obtained demographic, medical, and behavioral factors by self-administered questionnaire. They reviewed the findings on 48,500 men and 56,343 women aged 50 years and older in the 1990s who were followed through 2006. Almost all of the study subjects were white. The median baseline age was 67 years for women and 69 years for men.

The 14,647 deaths during follow-up included 5,410 cancer deaths, 4,942 cardiovascular deaths, 11,189 deaths resulting from respiratory disorders and 3,106 deaths from all other causes.

Any waist circumference greater than the smallest sizes (less than 90 cm in men or less than 75 cm in women) was associated with higher mortality. The mortality risk rose linearly with increasing waist circumference both in men and women.

Waist circumference was positively related to mortality in all patients. For men, the relative risk of mortality rose 16% (with normal BMI), 18% (overweight), and 21% (obese) with every 10-cm increase in waist size. For women, the relative risks with every 10-cm increase were greater for those with normal BMIs: 25% (normal), 15% (overweight), and 13% (obese).

When analyzed by cause of death, the link between waist circumference and mortality was strongest with death from respiratory causes, followed by cardiovascular disease and then cancer, Dr. Jacobs and his associates reported.

The investigators found no significant interactions between BMI-adjusted waist circumference and diabetes, smoking, or follow-up time. In addition, the researchers saw no interaction between waist circumference and hormone therapy in women. Relative mortality risks associated with waist circumference appeared to be greater in men who were less physically active.

“Results from this large prospective study emphasize the importance of waist circumference as a risk factor for mortality in older adults, regardless of whether the BMI is categorized as normal, overweight, or obese. Our results suggest that, regardless of weight, avoiding gains in waist circumference may reduce risk of premature mortality,” the researchers said.

The findings are important in light of the fact that current clinical guidelines do not address waist circumference in normal-weight patients and do not recommend weight loss for abdominally obese patients unless they have a high BMI, Dr. Jacobs and his associates noted.

The study was limited in that it included participants who were at least 50 years old, and it included very few nonwhite subjects. Thus, “results may not be generalizable to younger populations or those of other racial or ethnic backgrounds,” the authors noted.

Greater waist circumference was associated with a higher mortality risk independent of body mass index, according to a recent report.

Waist circumference is positively associated with mortality risk within all categories of BMI—normal, overweight, and obese. In fact, the relationship between greater waist circumference and higher mortality is strongest among women with a normal BMI, said Eric J. Jacobs, Ph.D., and his associates, who are with the epidemiology research program at the American Cancer Society in Atlanta.

The link between waist circumference and mortality has been reported in numerous studies, but this is the first study to examine that association within the standard categories of BMI, they noted (Arch. Intern. Med. 2010;170:1293-1301).

Dr. Jacobs and his colleagues used data from the Cancer Prevention Study II Nutrition Cohort, a large prospective study that obtained demographic, medical, and behavioral factors by self-administered questionnaire. They reviewed the findings on 48,500 men and 56,343 women aged 50 years and older in the 1990s who were followed through 2006. Almost all of the study subjects were white. The median baseline age was 67 years for women and 69 years for men.

The 14,647 deaths during follow-up included 5,410 cancer deaths, 4,942 cardiovascular deaths, 11,189 deaths resulting from respiratory disorders and 3,106 deaths from all other causes.

Any waist circumference greater than the smallest sizes (less than 90 cm in men or less than 75 cm in women) was associated with higher mortality. The mortality risk rose linearly with increasing waist circumference both in men and women.

Waist circumference was positively related to mortality in all patients. For men, the relative risk of mortality rose 16% (with normal BMI), 18% (overweight), and 21% (obese) with every 10-cm increase in waist size. For women, the relative risks with every 10-cm increase were greater for those with normal BMIs: 25% (normal), 15% (overweight), and 13% (obese).

When analyzed by cause of death, the link between waist circumference and mortality was strongest with death from respiratory causes, followed by cardiovascular disease and then cancer, Dr. Jacobs and his associates reported.

The investigators found no significant interactions between BMI-adjusted waist circumference and diabetes, smoking, or follow-up time. In addition, the researchers saw no interaction between waist circumference and hormone therapy in women. Relative mortality risks associated with waist circumference appeared to be greater in men who were less physically active.

“Results from this large prospective study emphasize the importance of waist circumference as a risk factor for mortality in older adults, regardless of whether the BMI is categorized as normal, overweight, or obese. Our results suggest that, regardless of weight, avoiding gains in waist circumference may reduce risk of premature mortality,” the researchers said.

The findings are important in light of the fact that current clinical guidelines do not address waist circumference in normal-weight patients and do not recommend weight loss for abdominally obese patients unless they have a high BMI, Dr. Jacobs and his associates noted.

The study was limited in that it included participants who were at least 50 years old, and it included very few nonwhite subjects. Thus, “results may not be generalizable to younger populations or those of other racial or ethnic backgrounds,” the authors noted.

Greater waist circumference was associated with a higher mortality risk independent of body mass index, according to a recent report.

Waist circumference is positively associated with mortality risk within all categories of BMI—normal, overweight, and obese. In fact, the relationship between greater waist circumference and higher mortality is strongest among women with a normal BMI, said Eric J. Jacobs, Ph.D., and his associates, who are with the epidemiology research program at the American Cancer Society in Atlanta.

The link between waist circumference and mortality has been reported in numerous studies, but this is the first study to examine that association within the standard categories of BMI, they noted (Arch. Intern. Med. 2010;170:1293-1301).

Dr. Jacobs and his colleagues used data from the Cancer Prevention Study II Nutrition Cohort, a large prospective study that obtained demographic, medical, and behavioral factors by self-administered questionnaire. They reviewed the findings on 48,500 men and 56,343 women aged 50 years and older in the 1990s who were followed through 2006. Almost all of the study subjects were white. The median baseline age was 67 years for women and 69 years for men.

The 14,647 deaths during follow-up included 5,410 cancer deaths, 4,942 cardiovascular deaths, 11,189 deaths resulting from respiratory disorders and 3,106 deaths from all other causes.

Any waist circumference greater than the smallest sizes (less than 90 cm in men or less than 75 cm in women) was associated with higher mortality. The mortality risk rose linearly with increasing waist circumference both in men and women.

Waist circumference was positively related to mortality in all patients. For men, the relative risk of mortality rose 16% (with normal BMI), 18% (overweight), and 21% (obese) with every 10-cm increase in waist size. For women, the relative risks with every 10-cm increase were greater for those with normal BMIs: 25% (normal), 15% (overweight), and 13% (obese).

When analyzed by cause of death, the link between waist circumference and mortality was strongest with death from respiratory causes, followed by cardiovascular disease and then cancer, Dr. Jacobs and his associates reported.

The investigators found no significant interactions between BMI-adjusted waist circumference and diabetes, smoking, or follow-up time. In addition, the researchers saw no interaction between waist circumference and hormone therapy in women. Relative mortality risks associated with waist circumference appeared to be greater in men who were less physically active.

“Results from this large prospective study emphasize the importance of waist circumference as a risk factor for mortality in older adults, regardless of whether the BMI is categorized as normal, overweight, or obese. Our results suggest that, regardless of weight, avoiding gains in waist circumference may reduce risk of premature mortality,” the researchers said.

The findings are important in light of the fact that current clinical guidelines do not address waist circumference in normal-weight patients and do not recommend weight loss for abdominally obese patients unless they have a high BMI, Dr. Jacobs and his associates noted.

The study was limited in that it included participants who were at least 50 years old, and it included very few nonwhite subjects. Thus, “results may not be generalizable to younger populations or those of other racial or ethnic backgrounds,” the authors noted.

Major Finding: Estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%, which extrapolates to 3.8% and 0.6% in the overall U.S. population.

Data Source: A nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

Disclosures: The investigators disclosed no conflicts of interest.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to an analysis of National Health and Nutrition Examination Survey data.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

The figures were derived from the most recent (2005-2008) NHANES data.

“Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

The estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema.

That translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A_1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC.

Major Finding: Estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%, which extrapolates to 3.8% and 0.6% in the overall U.S. population.

Data Source: A nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

Disclosures: The investigators disclosed no conflicts of interest.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to an analysis of National Health and Nutrition Examination Survey data.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

The figures were derived from the most recent (2005-2008) NHANES data.

“Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

The estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema.

That translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A_1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC.

Major Finding: Estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%, which extrapolates to 3.8% and 0.6% in the overall U.S. population.

Data Source: A nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

Disclosures: The investigators disclosed no conflicts of interest.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to an analysis of National Health and Nutrition Examination Survey data.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

The figures were derived from the most recent (2005-2008) NHANES data.

“Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

The estimated crude prevalence of diabetic retinopathy was 28.5% and that of vision-threatening retinopathy was 4.4%.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema.

That translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A_1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC.

Prophylactic mastectomy and salpingo-oophorectomy significantly decrease mortality as well as the risks of breast and ovarian cancer among women who carry BRCA1 or BRCA2 mutations, according to a report published in the Sept. 1 issue of JAMA .

These risk-reducing surgeries benefit both carriers who have not yet developed malignancies and those who have already been treated for breast or ovarian cancer and are still at risk for further primary disease, said Dr. Susan M. Domchek of the University of Pennsylvania, Philadelphia, and her associates.

Most previous studies that examined whether the prophylactic excisions actually impact mortality did not address their efficacy according to subjects’ mutation status or prior cancer diagnosis. With no proof of such efficacy, some clinicians and patients may have avoided the surgeries. Some may have believed that the excisions conferred little added protection against further malignancies, especially in the setting of chemotherapy-induced menopause or hormonal therapy, Dr. Domchek and her colleagues said.

The investigators assessed outcomes in a cohort of 2,482 BRCA1 and BRCA2 mutation carriers identified at 22 medical centers in North America and Europe that were participating in the Prevention and Observation of Surgical Endpoints (PROSE) consortium. The study subjects were enrolled in 1974-2008 and followed through the end of 2009 (median follow-up, 3.65 years).

Approximately 10% of these women underwent prophylactic mastectomy, and 40% underwent prophylactic salpingo-oophorectomy.

No breast cancers developed in mutation carriers who underwent prophylactic mastectomy, whereas breast cancers did develop in 7% of those who declined prophylactic mastectomy. This confirms that prophylactic mastectomy is highly effective at significantly reducing breast cancer in women at high risk, the investigators said (JAMA 2010;304:967-75).

Among women who underwent prophylactic salpingo-oophorectomy, only 1% subsequently developed ovarian cancer, and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic salpingo-oophorectomy, about 6% subsequently developed ovarian cancer, and 19% subsequently developed breast cancer.

Prophylactic salpingo-oophorectomy cut the risk of ovarian cancer by 70% in the subgroup of women who did not have prior breast cancer and decreased it even further, by 85%, in those who did have prior breast cancer. This finding illustrates why breast cancer patients may want to know about their BRCA mutation status even if they have undergone bilateral mastectomy: Prophylactic salpingo-oophorectomy may well protect them from developing a new primary malignancy in the ovaries.

Among women with no prior breast cancer, prophylactic salpingo-oophorectomy reduced breast cancer risk by 37% in carriers of the BRCA1 mutation and by 64% in carriers of the BRCA2 mutation.

Prophylactic salpingo-oophorectomy also decreased all-cause mortality, which was only 3% among women who underwent the procedure, compared with about 10% among those who did not. The prophylactic excision also significantly reduced breast cancer mortality (2% vs. 6%) and ovarian cancer mortality (0.4% vs. 3%), compared with no prophylactic salpingo-oophorectomy.

In an editorial accompanying this report, Dr. Laura Esserman and Dr. Virginia Kaklamani said that only 10% of the subjects in this study chose prophylactic mastectomy, and only 38% chose prophylactic salpingo-oophorectomy (JAMA 2010;304:1011-2). Now that the study results confirm that these procedures reduce not just cancer risk but also mortality, “women who test positive for BRCA1 or BRCA2 can make more informed choices about whether to consider prophylactic surgery or to opt for intensive surveillance,” and “women considering prophylactic interventions should be aware that options have changed and improved,” the physicians wrote.

Laparoscopic salpingo-oophorectomy in this setting is relatively low risk and can be done on an outpatient basis; invasive node sampling is no longer required as part of the procedure, said Dr. Esserman of the University of California, San Francisco, and Dr. Kaklamani of Northwestern University, Chicago.

Cosmetic options also have improved for prophylactic mastectomy. A total skin-sparing approach provides a more natural appearance, is safe and reliable, and now is routine in many major breast centers.

For women who worry that positive results on genetic testing will raise their insurance premiums, clinicians can reassure them that the Genetic Information Nondiscrimination Act of 2008 protects them from insurance and employer discrimination based on genetic profiles, said Dr. Esserman and Dr. Kaklamani.

Among the institutions providing support for the study were the University of Pennsylvania, the U.S. National Cancer Institute, the Cancer Genetics Network, the Dana-Farber/Harvard Cancer Center, and the U.K. National Institute for Health Research. Dr. Domchek, Dr. Esserman, and Dr. Kaklamani reported no financial conflicts of interest.

Prophylactic mastectomy and salpingo-oophorectomy significantly decrease mortality as well as the risks of breast and ovarian cancer among women who carry BRCA1 or BRCA2 mutations, according to a report published in the Sept. 1 issue of JAMA .

These risk-reducing surgeries benefit both carriers who have not yet developed malignancies and those who have already been treated for breast or ovarian cancer and are still at risk for further primary disease, said Dr. Susan M. Domchek of the University of Pennsylvania, Philadelphia, and her associates.

Most previous studies that examined whether the prophylactic excisions actually impact mortality did not address their efficacy according to subjects’ mutation status or prior cancer diagnosis. With no proof of such efficacy, some clinicians and patients may have avoided the surgeries. Some may have believed that the excisions conferred little added protection against further malignancies, especially in the setting of chemotherapy-induced menopause or hormonal therapy, Dr. Domchek and her colleagues said.

The investigators assessed outcomes in a cohort of 2,482 BRCA1 and BRCA2 mutation carriers identified at 22 medical centers in North America and Europe that were participating in the Prevention and Observation of Surgical Endpoints (PROSE) consortium. The study subjects were enrolled in 1974-2008 and followed through the end of 2009 (median follow-up, 3.65 years).

Approximately 10% of these women underwent prophylactic mastectomy, and 40% underwent prophylactic salpingo-oophorectomy.

No breast cancers developed in mutation carriers who underwent prophylactic mastectomy, whereas breast cancers did develop in 7% of those who declined prophylactic mastectomy. This confirms that prophylactic mastectomy is highly effective at significantly reducing breast cancer in women at high risk, the investigators said (JAMA 2010;304:967-75).

Among women who underwent prophylactic salpingo-oophorectomy, only 1% subsequently developed ovarian cancer, and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic salpingo-oophorectomy, about 6% subsequently developed ovarian cancer, and 19% subsequently developed breast cancer.

Prophylactic salpingo-oophorectomy cut the risk of ovarian cancer by 70% in the subgroup of women who did not have prior breast cancer and decreased it even further, by 85%, in those who did have prior breast cancer. This finding illustrates why breast cancer patients may want to know about their BRCA mutation status even if they have undergone bilateral mastectomy: Prophylactic salpingo-oophorectomy may well protect them from developing a new primary malignancy in the ovaries.

Among women with no prior breast cancer, prophylactic salpingo-oophorectomy reduced breast cancer risk by 37% in carriers of the BRCA1 mutation and by 64% in carriers of the BRCA2 mutation.

Prophylactic salpingo-oophorectomy also decreased all-cause mortality, which was only 3% among women who underwent the procedure, compared with about 10% among those who did not. The prophylactic excision also significantly reduced breast cancer mortality (2% vs. 6%) and ovarian cancer mortality (0.4% vs. 3%), compared with no prophylactic salpingo-oophorectomy.

In an editorial accompanying this report, Dr. Laura Esserman and Dr. Virginia Kaklamani said that only 10% of the subjects in this study chose prophylactic mastectomy, and only 38% chose prophylactic salpingo-oophorectomy (JAMA 2010;304:1011-2). Now that the study results confirm that these procedures reduce not just cancer risk but also mortality, “women who test positive for BRCA1 or BRCA2 can make more informed choices about whether to consider prophylactic surgery or to opt for intensive surveillance,” and “women considering prophylactic interventions should be aware that options have changed and improved,” the physicians wrote.

Laparoscopic salpingo-oophorectomy in this setting is relatively low risk and can be done on an outpatient basis; invasive node sampling is no longer required as part of the procedure, said Dr. Esserman of the University of California, San Francisco, and Dr. Kaklamani of Northwestern University, Chicago.

Cosmetic options also have improved for prophylactic mastectomy. A total skin-sparing approach provides a more natural appearance, is safe and reliable, and now is routine in many major breast centers.

For women who worry that positive results on genetic testing will raise their insurance premiums, clinicians can reassure them that the Genetic Information Nondiscrimination Act of 2008 protects them from insurance and employer discrimination based on genetic profiles, said Dr. Esserman and Dr. Kaklamani.

Among the institutions providing support for the study were the University of Pennsylvania, the U.S. National Cancer Institute, the Cancer Genetics Network, the Dana-Farber/Harvard Cancer Center, and the U.K. National Institute for Health Research. Dr. Domchek, Dr. Esserman, and Dr. Kaklamani reported no financial conflicts of interest.

Prophylactic mastectomy and salpingo-oophorectomy significantly decrease mortality as well as the risks of breast and ovarian cancer among women who carry BRCA1 or BRCA2 mutations, according to a report published in the Sept. 1 issue of JAMA .

These risk-reducing surgeries benefit both carriers who have not yet developed malignancies and those who have already been treated for breast or ovarian cancer and are still at risk for further primary disease, said Dr. Susan M. Domchek of the University of Pennsylvania, Philadelphia, and her associates.

Most previous studies that examined whether the prophylactic excisions actually impact mortality did not address their efficacy according to subjects’ mutation status or prior cancer diagnosis. With no proof of such efficacy, some clinicians and patients may have avoided the surgeries. Some may have believed that the excisions conferred little added protection against further malignancies, especially in the setting of chemotherapy-induced menopause or hormonal therapy, Dr. Domchek and her colleagues said.

The investigators assessed outcomes in a cohort of 2,482 BRCA1 and BRCA2 mutation carriers identified at 22 medical centers in North America and Europe that were participating in the Prevention and Observation of Surgical Endpoints (PROSE) consortium. The study subjects were enrolled in 1974-2008 and followed through the end of 2009 (median follow-up, 3.65 years).

Approximately 10% of these women underwent prophylactic mastectomy, and 40% underwent prophylactic salpingo-oophorectomy.

No breast cancers developed in mutation carriers who underwent prophylactic mastectomy, whereas breast cancers did develop in 7% of those who declined prophylactic mastectomy. This confirms that prophylactic mastectomy is highly effective at significantly reducing breast cancer in women at high risk, the investigators said (JAMA 2010;304:967-75).

Among women who underwent prophylactic salpingo-oophorectomy, only 1% subsequently developed ovarian cancer, and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic salpingo-oophorectomy, about 6% subsequently developed ovarian cancer, and 19% subsequently developed breast cancer.

Prophylactic salpingo-oophorectomy cut the risk of ovarian cancer by 70% in the subgroup of women who did not have prior breast cancer and decreased it even further, by 85%, in those who did have prior breast cancer. This finding illustrates why breast cancer patients may want to know about their BRCA mutation status even if they have undergone bilateral mastectomy: Prophylactic salpingo-oophorectomy may well protect them from developing a new primary malignancy in the ovaries.

Among women with no prior breast cancer, prophylactic salpingo-oophorectomy reduced breast cancer risk by 37% in carriers of the BRCA1 mutation and by 64% in carriers of the BRCA2 mutation.

Prophylactic salpingo-oophorectomy also decreased all-cause mortality, which was only 3% among women who underwent the procedure, compared with about 10% among those who did not. The prophylactic excision also significantly reduced breast cancer mortality (2% vs. 6%) and ovarian cancer mortality (0.4% vs. 3%), compared with no prophylactic salpingo-oophorectomy.

In an editorial accompanying this report, Dr. Laura Esserman and Dr. Virginia Kaklamani said that only 10% of the subjects in this study chose prophylactic mastectomy, and only 38% chose prophylactic salpingo-oophorectomy (JAMA 2010;304:1011-2). Now that the study results confirm that these procedures reduce not just cancer risk but also mortality, “women who test positive for BRCA1 or BRCA2 can make more informed choices about whether to consider prophylactic surgery or to opt for intensive surveillance,” and “women considering prophylactic interventions should be aware that options have changed and improved,” the physicians wrote.

Laparoscopic salpingo-oophorectomy in this setting is relatively low risk and can be done on an outpatient basis; invasive node sampling is no longer required as part of the procedure, said Dr. Esserman of the University of California, San Francisco, and Dr. Kaklamani of Northwestern University, Chicago.

Cosmetic options also have improved for prophylactic mastectomy. A total skin-sparing approach provides a more natural appearance, is safe and reliable, and now is routine in many major breast centers.

For women who worry that positive results on genetic testing will raise their insurance premiums, clinicians can reassure them that the Genetic Information Nondiscrimination Act of 2008 protects them from insurance and employer discrimination based on genetic profiles, said Dr. Esserman and Dr. Kaklamani.

Among the institutions providing support for the study were the University of Pennsylvania, the U.S. National Cancer Institute, the Cancer Genetics Network, the Dana-Farber/Harvard Cancer Center, and the U.K. National Institute for Health Research. Dr. Domchek, Dr. Esserman, and Dr. Kaklamani reported no financial conflicts of interest.

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, according to a report in the Sept. 1 issue of JAMA.

This indicates that there is “a robust U-shaped association” between CP risk and gestational age, not just for deliveries during the whole of pregnancy but also for deliveries at term, 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.

The investigators 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.

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, according to a report in the Sept. 1 issue of JAMA.

This indicates that there is “a robust U-shaped association” between CP risk and gestational age, not just for deliveries during the whole of pregnancy but also for deliveries at term, 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.

The investigators 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.

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, according to a report in the Sept. 1 issue of JAMA.

This indicates that there is “a robust U-shaped association” between CP risk and gestational age, not just for deliveries during the whole of pregnancy but also for deliveries at term, 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.

The investigators 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.

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.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to a report in the Aug. 11 issue of JAMA.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

These figures were derived from the most recent (2005-2008) National Health and Nutrition Examination Survey (NHANES) data. “Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema. This translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican-American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC. The authors reported no financial conflicts of interest.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to a report in the Aug. 11 issue of JAMA.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

These figures were derived from the most recent (2005-2008) National Health and Nutrition Examination Survey (NHANES) data. “Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema. This translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican-American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC. The authors reported no financial conflicts of interest.

The estimated prevalence of diabetic retinopathy is about 29% in U.S. adults aged 40 years and older who have diabetes, according to a report in the Aug. 11 issue of JAMA.

The estimated prevalence of vision-threatening retinopathy in the same population is about 4%.

These figures were derived from the most recent (2005-2008) National Health and Nutrition Examination Survey (NHANES) data. “Despite the documented increase in the prevalence of diabetes in the U.S. population, national population-based data on the prevalence and severity of diabetic retinopathy remain scarce, with previous nationwide prevalence estimates dating back to 1988-1994,” said Dr. Xinzhi Zhang of the Centers for Disease Control and Prevention, Atlanta, and his associates.

The investigators based their analysis on a nationally representative sample of 1,006 patients with diabetes who were aged 40 or older when they underwent ophthalmic digital fundus photography as part of the NHANES study.

“Extrapolating to the overall U.S. population in the same period, the prevalences nationwide would be 3.8% and 0.6%,” the investigators wrote (JAMA 2010;304:649-56).

About 1.5% of the study subjects had proliferative diabetic retinopathy and 2.7% had clinically significant macular edema. This translates to rates of 0.2% and 0.4%, respectively, in the general U.S. population.

In the study subjects, there was no significant difference in the rates of retinopathy between patients aged 40-64 years and those aged 65 years and older.

Men were found to have a higher rate of retinopathy (31.6%) than women (25.7%).

Compared with white study subjects, members of minority groups were more likely to have diabetic retinopathy. The rate was 26.4% in whites, compared with 38.8% in black subjects, and 34% in Mexican-American subjects.

As expected, subjects who used insulin and those with higher hemoglobin A1c levels, longer duration of diabetes, and higher blood pressure all were more likely to have retinopathy than were those who did not have these risk factors.

This updated information shows that there is a high prevalence of diabetic retinopathy and a high prevalence of vision-threatening diabetic retinopathy in the United States, particularly in men and racial/ethnic minorities, the authors concluded.

The study was supported by the National Center for Health Statistics and the National Eye Institute, in addition to the CDC. The authors reported no financial conflicts of interest.

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis reported in the Aug. 11 issue of JAMA.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen’s University Belfast, Ireland, and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” they noted.

Dr. Cardwell and his colleagues searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world’s largest computerised database of anonymised longitudinal medical records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

They reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice. During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined. This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H2 receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion ... we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

“These drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use,” they said.

Access to the GPRD database was funded by the Medical Research Council. No financial conflicts of interest were reported.

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis reported in the Aug. 11 issue of JAMA.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen’s University Belfast, Ireland, and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” they noted.

Dr. Cardwell and his colleagues searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world’s largest computerised database of anonymised longitudinal medical records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

They reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice. During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined. This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H2 receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion ... we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

“These drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use,” they said.

Access to the GPRD database was funded by the Medical Research Council. No financial conflicts of interest were reported.

The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis reported in the Aug. 11 issue of JAMA.

Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen’s University Belfast, Ireland, and his associates.

“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” they noted.

Dr. Cardwell and his colleagues searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world’s largest computerised database of anonymised longitudinal medical records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.

They reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice. During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.

There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined. This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H2 receptor antagonists.

Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).

In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.

There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.

Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.

“In conclusion ... we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.

“These drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use,” they said.

Access to the GPRD database was funded by the Medical Research Council. No financial conflicts of interest were reported.