Mary Ann Moon

Hormonal contraceptives don’t appear to increase the risk of recurrence of venous thromboembolism among women taking anticoagulants, according to a report published in Blood.

Clinicians are often reluctant to prescribe hormonal contraceptives for women who develop venous thromboembolism (VTE) because the drugs are known to raise the risk of VTE and are considered to be contraindicated in either active or previous VTE. But effective contraception is necessary for women of childbearing age who are taking anticoagulants, because these drugs cross the placenta and could cause fetal bleeding and other adverse events, wrote Dr. Ida Martinelli of the A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, and her associates (Blood 2016;127[11]:1417-25).

©ThinkStockPhotos.com

Adding further to the confusion, World Health Organization guidelines state that estrogen-containing contraceptives confer “an unacceptable health risk” during anticoagulant therapy for VTE, but the International Society on Thrombosis and Haemostasis recommends that women diagnosed with VTE continue oral contraceptive and estrogen-replacement hormonal therapy until they discontinue anticoagulant therapy “because any prothrombotic effect of hormonal therapy is likely to be suppressed by therapeutic-intensity anticoagulation,” the investigators noted.

In the current study, the investigators performed a secondary analysis of data accrued in two large trials evaluating rivaroxaban versus enoxaparin plus vitamin K antagonists, which involved 1,888 women younger than age 60 (mean age, 41 years) who were being treated for acute deep vein thrombosis or acute pulmonary embolism. A total of 402 of these women used hormonal therapy during the 4-year studies.

There were 7 VTE recurrences during hormonal contraceptive use and 38 without hormonal contraceptive use. The incidence densities were 3.7% per year with hormonal therapy and 4.7% per year without it, for a hazard ratio of 0.56.

This indicates that hormonal contraceptive use did not make a clinically important difference in the rate of VTE recurrence. Moreover, these findings were consistent regardless of whether the contraceptives contained estrogen (incidence density, 3.7% per year) or progestin only (incidence density, 3.8% per year), and remained consistent in sensitivity analyses.

“These results challenge the WHO guidelines and instead support the International Society on Thrombosis and Haemostasis recommendations,” the investigators wrote.

“Our finding of similar risks of recurrent VTE for women who did or did not receive hormonal therapy, whether progestin-only or estrogen-containing therapy, supports a treatment selection that incorporates patient preference, including the choice of estrogen-containing contraception,” they added.

The study was funded in part by Bayer Healthcare Pharmaceuticals, which also provided editorial assistance. Dr. Martinelli reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.

Hormonal contraceptives don’t appear to increase the risk of recurrence of venous thromboembolism among women taking anticoagulants, according to a report published in Blood.

Clinicians are often reluctant to prescribe hormonal contraceptives for women who develop venous thromboembolism (VTE) because the drugs are known to raise the risk of VTE and are considered to be contraindicated in either active or previous VTE. But effective contraception is necessary for women of childbearing age who are taking anticoagulants, because these drugs cross the placenta and could cause fetal bleeding and other adverse events, wrote Dr. Ida Martinelli of the A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, and her associates (Blood 2016;127[11]:1417-25).

©ThinkStockPhotos.com

Adding further to the confusion, World Health Organization guidelines state that estrogen-containing contraceptives confer “an unacceptable health risk” during anticoagulant therapy for VTE, but the International Society on Thrombosis and Haemostasis recommends that women diagnosed with VTE continue oral contraceptive and estrogen-replacement hormonal therapy until they discontinue anticoagulant therapy “because any prothrombotic effect of hormonal therapy is likely to be suppressed by therapeutic-intensity anticoagulation,” the investigators noted.

In the current study, the investigators performed a secondary analysis of data accrued in two large trials evaluating rivaroxaban versus enoxaparin plus vitamin K antagonists, which involved 1,888 women younger than age 60 (mean age, 41 years) who were being treated for acute deep vein thrombosis or acute pulmonary embolism. A total of 402 of these women used hormonal therapy during the 4-year studies.

There were 7 VTE recurrences during hormonal contraceptive use and 38 without hormonal contraceptive use. The incidence densities were 3.7% per year with hormonal therapy and 4.7% per year without it, for a hazard ratio of 0.56.

This indicates that hormonal contraceptive use did not make a clinically important difference in the rate of VTE recurrence. Moreover, these findings were consistent regardless of whether the contraceptives contained estrogen (incidence density, 3.7% per year) or progestin only (incidence density, 3.8% per year), and remained consistent in sensitivity analyses.

“These results challenge the WHO guidelines and instead support the International Society on Thrombosis and Haemostasis recommendations,” the investigators wrote.

“Our finding of similar risks of recurrent VTE for women who did or did not receive hormonal therapy, whether progestin-only or estrogen-containing therapy, supports a treatment selection that incorporates patient preference, including the choice of estrogen-containing contraception,” they added.

The study was funded in part by Bayer Healthcare Pharmaceuticals, which also provided editorial assistance. Dr. Martinelli reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.

Hormonal contraceptives don’t appear to increase the risk of recurrence of venous thromboembolism among women taking anticoagulants, according to a report published in Blood.

Clinicians are often reluctant to prescribe hormonal contraceptives for women who develop venous thromboembolism (VTE) because the drugs are known to raise the risk of VTE and are considered to be contraindicated in either active or previous VTE. But effective contraception is necessary for women of childbearing age who are taking anticoagulants, because these drugs cross the placenta and could cause fetal bleeding and other adverse events, wrote Dr. Ida Martinelli of the A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, and her associates (Blood 2016;127[11]:1417-25).

©ThinkStockPhotos.com

Adding further to the confusion, World Health Organization guidelines state that estrogen-containing contraceptives confer “an unacceptable health risk” during anticoagulant therapy for VTE, but the International Society on Thrombosis and Haemostasis recommends that women diagnosed with VTE continue oral contraceptive and estrogen-replacement hormonal therapy until they discontinue anticoagulant therapy “because any prothrombotic effect of hormonal therapy is likely to be suppressed by therapeutic-intensity anticoagulation,” the investigators noted.

In the current study, the investigators performed a secondary analysis of data accrued in two large trials evaluating rivaroxaban versus enoxaparin plus vitamin K antagonists, which involved 1,888 women younger than age 60 (mean age, 41 years) who were being treated for acute deep vein thrombosis or acute pulmonary embolism. A total of 402 of these women used hormonal therapy during the 4-year studies.

There were 7 VTE recurrences during hormonal contraceptive use and 38 without hormonal contraceptive use. The incidence densities were 3.7% per year with hormonal therapy and 4.7% per year without it, for a hazard ratio of 0.56.

This indicates that hormonal contraceptive use did not make a clinically important difference in the rate of VTE recurrence. Moreover, these findings were consistent regardless of whether the contraceptives contained estrogen (incidence density, 3.7% per year) or progestin only (incidence density, 3.8% per year), and remained consistent in sensitivity analyses.

“These results challenge the WHO guidelines and instead support the International Society on Thrombosis and Haemostasis recommendations,” the investigators wrote.

“Our finding of similar risks of recurrent VTE for women who did or did not receive hormonal therapy, whether progestin-only or estrogen-containing therapy, supports a treatment selection that incorporates patient preference, including the choice of estrogen-containing contraception,” they added.

The study was funded in part by Bayer Healthcare Pharmaceuticals, which also provided editorial assistance. Dr. Martinelli reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.

Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.

The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.

They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.

Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.

Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).

Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).

This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.

Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.

The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.

They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.

Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.

Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).

Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).

This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.

Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.

The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.

They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.

Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.

Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).

Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).

This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.

Bisphenol S (BPS), commonly used as a “safe” substitute for bisphenol A (BPA) in the manufacturing of plastics and other consumer products, induces lipid accumulation in, and differentiation of, human preadipocytes, indicating that it may have adverse effects on the endocrine system, according to a report published online March 22 in Endocrinology.

The findings suggest that BPS is not a harmless substitute for BPA and that more thorough toxicologic and epidemiologic studies are warranted regarding its effects on human health, said Jonathan G. Boucher and his associates at the Environmental Health Science and Research Bureau, Health Canada, Ottawa.

Ugreen/Thinkstock.com

BPS is a close analogue of BPA and has been detected in many products, including paper receipts, canned foods and drinks, epoxy resins, and baby bottles, as well as in environmental samples such as indoor dust. It is known to exhibit estrogenic activity and was suspected of involvement in lipid processes that also entail hormonal cues from glucocorticoids and insulin.

In a series of laboratory analyses, the investigators examined the effects of BPS on primary human preadipocytes harvested from the hips, thighs, and abdomens of normal-weight female donors aged 25-57 years. They confirmed that BPS has estrogenic effects. They also reported for the first time that, “similar to BPA, BPS increases adipogenesis in human preadipocytes” by almost twofold and induces adipocyte differentiation, primarily by activating the adipogenic transcription factor PPARG (peroxisome proliferator-activated receptor-gamma).

“Further study is required to better understand potential hazards of widespread BPS exposure. The few reports available now indicate that BPS can affect endocrine function, as demonstrated by studies showing decreased testosterone, androstenedione, and cortisol levels in ex vivo and in vitro models,” the investigators noted (Endocrinol. 2016 Mar 22. doi:10.1210/en.2015-1872) .

Bisphenol S (BPS), commonly used as a “safe” substitute for bisphenol A (BPA) in the manufacturing of plastics and other consumer products, induces lipid accumulation in, and differentiation of, human preadipocytes, indicating that it may have adverse effects on the endocrine system, according to a report published online March 22 in Endocrinology.

The findings suggest that BPS is not a harmless substitute for BPA and that more thorough toxicologic and epidemiologic studies are warranted regarding its effects on human health, said Jonathan G. Boucher and his associates at the Environmental Health Science and Research Bureau, Health Canada, Ottawa.

Ugreen/Thinkstock.com

BPS is a close analogue of BPA and has been detected in many products, including paper receipts, canned foods and drinks, epoxy resins, and baby bottles, as well as in environmental samples such as indoor dust. It is known to exhibit estrogenic activity and was suspected of involvement in lipid processes that also entail hormonal cues from glucocorticoids and insulin.

In a series of laboratory analyses, the investigators examined the effects of BPS on primary human preadipocytes harvested from the hips, thighs, and abdomens of normal-weight female donors aged 25-57 years. They confirmed that BPS has estrogenic effects. They also reported for the first time that, “similar to BPA, BPS increases adipogenesis in human preadipocytes” by almost twofold and induces adipocyte differentiation, primarily by activating the adipogenic transcription factor PPARG (peroxisome proliferator-activated receptor-gamma).

“Further study is required to better understand potential hazards of widespread BPS exposure. The few reports available now indicate that BPS can affect endocrine function, as demonstrated by studies showing decreased testosterone, androstenedione, and cortisol levels in ex vivo and in vitro models,” the investigators noted (Endocrinol. 2016 Mar 22. doi:10.1210/en.2015-1872) .

Bisphenol S (BPS), commonly used as a “safe” substitute for bisphenol A (BPA) in the manufacturing of plastics and other consumer products, induces lipid accumulation in, and differentiation of, human preadipocytes, indicating that it may have adverse effects on the endocrine system, according to a report published online March 22 in Endocrinology.

The findings suggest that BPS is not a harmless substitute for BPA and that more thorough toxicologic and epidemiologic studies are warranted regarding its effects on human health, said Jonathan G. Boucher and his associates at the Environmental Health Science and Research Bureau, Health Canada, Ottawa.

Ugreen/Thinkstock.com

BPS is a close analogue of BPA and has been detected in many products, including paper receipts, canned foods and drinks, epoxy resins, and baby bottles, as well as in environmental samples such as indoor dust. It is known to exhibit estrogenic activity and was suspected of involvement in lipid processes that also entail hormonal cues from glucocorticoids and insulin.

In a series of laboratory analyses, the investigators examined the effects of BPS on primary human preadipocytes harvested from the hips, thighs, and abdomens of normal-weight female donors aged 25-57 years. They confirmed that BPS has estrogenic effects. They also reported for the first time that, “similar to BPA, BPS increases adipogenesis in human preadipocytes” by almost twofold and induces adipocyte differentiation, primarily by activating the adipogenic transcription factor PPARG (peroxisome proliferator-activated receptor-gamma).

“Further study is required to better understand potential hazards of widespread BPS exposure. The few reports available now indicate that BPS can affect endocrine function, as demonstrated by studies showing decreased testosterone, androstenedione, and cortisol levels in ex vivo and in vitro models,” the investigators noted (Endocrinol. 2016 Mar 22. doi:10.1210/en.2015-1872) .

Combination therapy with sulindac and erlotinib reduced the burden of duodenal polyps in a preliminary study involving 92 patients with familial adenomatous polyposis (FAP), which was reported online March 22 in JAMA.

At present, surgery – including repeated polypectomies, duodenectomy, and the Whipple procedure – are the standard of care for advanced neoplasia of the duodenum, but they are associated with marked morbidity and mortality. “Our study suggests the possibility of an effective chemoprevention strategy for duodenal neoplasia in patients with FAP,” said Dr. N. Jewel Samadder of the Huntsman Cancer Institute and the department of gastroenterology at the University of Utah, Salt Lake City, and his associates.

Given the preliminary nature of this study, especially the relatively small study population and the relatively short (6-month) follow-up, further research is crucial. It will be particularly important to determine whether this decline in the burden of duodenal polyps translates into more definitive, clinically meaningful endpoints such as preventing the formation of new polyps and preventing malignant transformation. Optimal dosing, treatment resistance, and long-term adverse effects also must be investigated further, the investigators noted.

They assessed the effects of 6 months of combination therapy using the cyclooxygenase inhibitor sulindac (150 mg twice daily) plus the epidermal

growth factor receptor (EGFR) inhibitor erlotinib (75 mg daily), compared with matching placebos, in a single-center randomized double-blind study. The study was halted after an interim analysis showed the clear superiority of active treatment over placebo.

The primary outcome was change in duodenal polyp burden as detected on endoscopy, defined as the total number and diameter of all polyps in a 10-cm segment of the duodenum. The sulindac-erlotinib group showed a median decrease of 8.5 mm in polyp burden at 6 months, while the placebo group showed a median 8-mm increase. This represents a 37.9% decrease in polyp burden with active treatment and a 30.6% increase with placebo, Dr. Samadder and his associates said (JAMA. 2016 Mar 22. doi: 10.1001/jama.2016.2522).

These results remained consistent in a subgroup analysis comparing patients with classic FAP against those with attenuated FAP, in a subgroup analysis comparing patients with a low initial polyp burden against those with a high initial polyp burden, and in a subgroup analysis involving only the 81 patients with a confirmed germline mutation in the adenomatous polyposis coli (APC) gene.

However, the rate of adverse events associated with active treatment was high. An acneform rash developed in 87% of participants taking sulindac-erlotinib and oral mucositis developed in 39%. Nineteen patients withdrew from the study, including five who reported adverse events or possible allergic reactions to active treatment, and 54% required a dose reduction of sulindac, erlotinib, or both. “Dose-ranging studies will be needed to determine if lower and/or less-frequent dosing could diminish these adverse effects but retain efficacy,” the investigators said.

Combination therapy with sulindac and erlotinib reduced the burden of duodenal polyps in a preliminary study involving 92 patients with familial adenomatous polyposis (FAP), which was reported online March 22 in JAMA.

At present, surgery – including repeated polypectomies, duodenectomy, and the Whipple procedure – are the standard of care for advanced neoplasia of the duodenum, but they are associated with marked morbidity and mortality. “Our study suggests the possibility of an effective chemoprevention strategy for duodenal neoplasia in patients with FAP,” said Dr. N. Jewel Samadder of the Huntsman Cancer Institute and the department of gastroenterology at the University of Utah, Salt Lake City, and his associates.

Given the preliminary nature of this study, especially the relatively small study population and the relatively short (6-month) follow-up, further research is crucial. It will be particularly important to determine whether this decline in the burden of duodenal polyps translates into more definitive, clinically meaningful endpoints such as preventing the formation of new polyps and preventing malignant transformation. Optimal dosing, treatment resistance, and long-term adverse effects also must be investigated further, the investigators noted.

They assessed the effects of 6 months of combination therapy using the cyclooxygenase inhibitor sulindac (150 mg twice daily) plus the epidermal

growth factor receptor (EGFR) inhibitor erlotinib (75 mg daily), compared with matching placebos, in a single-center randomized double-blind study. The study was halted after an interim analysis showed the clear superiority of active treatment over placebo.

The primary outcome was change in duodenal polyp burden as detected on endoscopy, defined as the total number and diameter of all polyps in a 10-cm segment of the duodenum. The sulindac-erlotinib group showed a median decrease of 8.5 mm in polyp burden at 6 months, while the placebo group showed a median 8-mm increase. This represents a 37.9% decrease in polyp burden with active treatment and a 30.6% increase with placebo, Dr. Samadder and his associates said (JAMA. 2016 Mar 22. doi: 10.1001/jama.2016.2522).

These results remained consistent in a subgroup analysis comparing patients with classic FAP against those with attenuated FAP, in a subgroup analysis comparing patients with a low initial polyp burden against those with a high initial polyp burden, and in a subgroup analysis involving only the 81 patients with a confirmed germline mutation in the adenomatous polyposis coli (APC) gene.

However, the rate of adverse events associated with active treatment was high. An acneform rash developed in 87% of participants taking sulindac-erlotinib and oral mucositis developed in 39%. Nineteen patients withdrew from the study, including five who reported adverse events or possible allergic reactions to active treatment, and 54% required a dose reduction of sulindac, erlotinib, or both. “Dose-ranging studies will be needed to determine if lower and/or less-frequent dosing could diminish these adverse effects but retain efficacy,” the investigators said.

Combination therapy with sulindac and erlotinib reduced the burden of duodenal polyps in a preliminary study involving 92 patients with familial adenomatous polyposis (FAP), which was reported online March 22 in JAMA.

At present, surgery – including repeated polypectomies, duodenectomy, and the Whipple procedure – are the standard of care for advanced neoplasia of the duodenum, but they are associated with marked morbidity and mortality. “Our study suggests the possibility of an effective chemoprevention strategy for duodenal neoplasia in patients with FAP,” said Dr. N. Jewel Samadder of the Huntsman Cancer Institute and the department of gastroenterology at the University of Utah, Salt Lake City, and his associates.

Given the preliminary nature of this study, especially the relatively small study population and the relatively short (6-month) follow-up, further research is crucial. It will be particularly important to determine whether this decline in the burden of duodenal polyps translates into more definitive, clinically meaningful endpoints such as preventing the formation of new polyps and preventing malignant transformation. Optimal dosing, treatment resistance, and long-term adverse effects also must be investigated further, the investigators noted.

They assessed the effects of 6 months of combination therapy using the cyclooxygenase inhibitor sulindac (150 mg twice daily) plus the epidermal

growth factor receptor (EGFR) inhibitor erlotinib (75 mg daily), compared with matching placebos, in a single-center randomized double-blind study. The study was halted after an interim analysis showed the clear superiority of active treatment over placebo.

The primary outcome was change in duodenal polyp burden as detected on endoscopy, defined as the total number and diameter of all polyps in a 10-cm segment of the duodenum. The sulindac-erlotinib group showed a median decrease of 8.5 mm in polyp burden at 6 months, while the placebo group showed a median 8-mm increase. This represents a 37.9% decrease in polyp burden with active treatment and a 30.6% increase with placebo, Dr. Samadder and his associates said (JAMA. 2016 Mar 22. doi: 10.1001/jama.2016.2522).

These results remained consistent in a subgroup analysis comparing patients with classic FAP against those with attenuated FAP, in a subgroup analysis comparing patients with a low initial polyp burden against those with a high initial polyp burden, and in a subgroup analysis involving only the 81 patients with a confirmed germline mutation in the adenomatous polyposis coli (APC) gene.

However, the rate of adverse events associated with active treatment was high. An acneform rash developed in 87% of participants taking sulindac-erlotinib and oral mucositis developed in 39%. Nineteen patients withdrew from the study, including five who reported adverse events or possible allergic reactions to active treatment, and 54% required a dose reduction of sulindac, erlotinib, or both. “Dose-ranging studies will be needed to determine if lower and/or less-frequent dosing could diminish these adverse effects but retain efficacy,” the investigators said.

Multidisciplinary care integrating urology, medical oncology, and radiation oncology expertise is the key to providing the best care for patients with metastatic or muscle-invasive bladder cancer, the American Society of Clinical Oncology (ASCO) said in its endorsement of a new clinical practice guideline developed by the European Association of Urology (EAU).

ASCO’s clinical practice guideline committee reviewed the EAU’s recommendations and found them “clear, thorough, based on the most relevant scientific evidence, and ... acceptable to patients.” It endorsed all but one of the EAU’s recommendations, with what it described as only minor qualifications “to better clarify the roles for systemic chemotherapy- and chemoradiotherapy-based organ preservation treatment.”

©Sebastian Kaulitzki/ thinkstockphotos.com

By endorsing the EAU’s guideline, ASCO hopes to “increase the number of high-quality, ASCO-vetted guidelines available” to its membership and to all primary-care providers, urologists, radiation oncologists, and medical oncologists, said Dr. Matthew I. Milowsky of the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, and his associates on the ASCO clinical practice guideline committee.

Approximately 5% of all patients newly diagnosed as having bladder cancer present with metastatic disease. Another 30% present with muscle-invasive disease, and approximately half of them will eventually develop distant metastases.

In particular, the ASCO committee agreed that the importance of multidisciplinary care “cannot be overemphasized,” given the lethality of metastatic and muscle-invasive bladder cancer and their severe impact on patients’ quality of life. For example, patients should be referred to a medical oncologist for a discussion of neoadjuvant chemotherapy, and those with muscle-invasive disease should be referred to a radiation oncologist for a discussion of bladder preservation.

ASCO also emphasizes that radiotherapy alone is inferior to chemoradiotherapy in patients receiving bladder-preservation therapy with curative intent, and that chemoradiotherapy should be recommended.

For high-risk patients who haven’t received the recommended neoadjuvant chemotherapy, adjuvant cisplatin-based chemotherapy is an option. But the data are insufficient to consider the use of non-cisplatin-based chemotherapy in the adjuvant setting, Dr. Milowsky and his associates said (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.65.9797).

There is no FDA-approved therapy for patients with metastatic bladder cancer who show disease progression after platinum-based combination chemotherapy. These patients should be encouraged to participate in clinical trials, where they can access promising experimental treatments such as molecular-targeting agents and immunotherapies. Alternatively, they can be offered single-agent therapy such as paclitaxel, docetaxel, or vinflunine where available.

The one recommendation in the EAU guideline that ASCO did not endorse stated that preoperative radiotherapy for muscle-invasive bladder cancer “can result in tumor downstaging after 4-6 weeks.” ASCO’s clinical practice guideline committee determined that the evidence on which the EAU based this recommendation was not sufficient.

Multidisciplinary care integrating urology, medical oncology, and radiation oncology expertise is the key to providing the best care for patients with metastatic or muscle-invasive bladder cancer, the American Society of Clinical Oncology (ASCO) said in its endorsement of a new clinical practice guideline developed by the European Association of Urology (EAU).

ASCO’s clinical practice guideline committee reviewed the EAU’s recommendations and found them “clear, thorough, based on the most relevant scientific evidence, and ... acceptable to patients.” It endorsed all but one of the EAU’s recommendations, with what it described as only minor qualifications “to better clarify the roles for systemic chemotherapy- and chemoradiotherapy-based organ preservation treatment.”

©Sebastian Kaulitzki/ thinkstockphotos.com

By endorsing the EAU’s guideline, ASCO hopes to “increase the number of high-quality, ASCO-vetted guidelines available” to its membership and to all primary-care providers, urologists, radiation oncologists, and medical oncologists, said Dr. Matthew I. Milowsky of the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, and his associates on the ASCO clinical practice guideline committee.

Approximately 5% of all patients newly diagnosed as having bladder cancer present with metastatic disease. Another 30% present with muscle-invasive disease, and approximately half of them will eventually develop distant metastases.

In particular, the ASCO committee agreed that the importance of multidisciplinary care “cannot be overemphasized,” given the lethality of metastatic and muscle-invasive bladder cancer and their severe impact on patients’ quality of life. For example, patients should be referred to a medical oncologist for a discussion of neoadjuvant chemotherapy, and those with muscle-invasive disease should be referred to a radiation oncologist for a discussion of bladder preservation.

ASCO also emphasizes that radiotherapy alone is inferior to chemoradiotherapy in patients receiving bladder-preservation therapy with curative intent, and that chemoradiotherapy should be recommended.

For high-risk patients who haven’t received the recommended neoadjuvant chemotherapy, adjuvant cisplatin-based chemotherapy is an option. But the data are insufficient to consider the use of non-cisplatin-based chemotherapy in the adjuvant setting, Dr. Milowsky and his associates said (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.65.9797).

There is no FDA-approved therapy for patients with metastatic bladder cancer who show disease progression after platinum-based combination chemotherapy. These patients should be encouraged to participate in clinical trials, where they can access promising experimental treatments such as molecular-targeting agents and immunotherapies. Alternatively, they can be offered single-agent therapy such as paclitaxel, docetaxel, or vinflunine where available.

The one recommendation in the EAU guideline that ASCO did not endorse stated that preoperative radiotherapy for muscle-invasive bladder cancer “can result in tumor downstaging after 4-6 weeks.” ASCO’s clinical practice guideline committee determined that the evidence on which the EAU based this recommendation was not sufficient.

Multidisciplinary care integrating urology, medical oncology, and radiation oncology expertise is the key to providing the best care for patients with metastatic or muscle-invasive bladder cancer, the American Society of Clinical Oncology (ASCO) said in its endorsement of a new clinical practice guideline developed by the European Association of Urology (EAU).

ASCO’s clinical practice guideline committee reviewed the EAU’s recommendations and found them “clear, thorough, based on the most relevant scientific evidence, and ... acceptable to patients.” It endorsed all but one of the EAU’s recommendations, with what it described as only minor qualifications “to better clarify the roles for systemic chemotherapy- and chemoradiotherapy-based organ preservation treatment.”

©Sebastian Kaulitzki/ thinkstockphotos.com

By endorsing the EAU’s guideline, ASCO hopes to “increase the number of high-quality, ASCO-vetted guidelines available” to its membership and to all primary-care providers, urologists, radiation oncologists, and medical oncologists, said Dr. Matthew I. Milowsky of the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, and his associates on the ASCO clinical practice guideline committee.

Approximately 5% of all patients newly diagnosed as having bladder cancer present with metastatic disease. Another 30% present with muscle-invasive disease, and approximately half of them will eventually develop distant metastases.

In particular, the ASCO committee agreed that the importance of multidisciplinary care “cannot be overemphasized,” given the lethality of metastatic and muscle-invasive bladder cancer and their severe impact on patients’ quality of life. For example, patients should be referred to a medical oncologist for a discussion of neoadjuvant chemotherapy, and those with muscle-invasive disease should be referred to a radiation oncologist for a discussion of bladder preservation.

ASCO also emphasizes that radiotherapy alone is inferior to chemoradiotherapy in patients receiving bladder-preservation therapy with curative intent, and that chemoradiotherapy should be recommended.

For high-risk patients who haven’t received the recommended neoadjuvant chemotherapy, adjuvant cisplatin-based chemotherapy is an option. But the data are insufficient to consider the use of non-cisplatin-based chemotherapy in the adjuvant setting, Dr. Milowsky and his associates said (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.65.9797).

There is no FDA-approved therapy for patients with metastatic bladder cancer who show disease progression after platinum-based combination chemotherapy. These patients should be encouraged to participate in clinical trials, where they can access promising experimental treatments such as molecular-targeting agents and immunotherapies. Alternatively, they can be offered single-agent therapy such as paclitaxel, docetaxel, or vinflunine where available.

The one recommendation in the EAU guideline that ASCO did not endorse stated that preoperative radiotherapy for muscle-invasive bladder cancer “can result in tumor downstaging after 4-6 weeks.” ASCO’s clinical practice guideline committee determined that the evidence on which the EAU based this recommendation was not sufficient.

Young transgender women have a high prevalence of psychiatric disorders that is two to four times higher than that in the general population, according to a report published online March 21 in JAMA Pediatrics.

“Improving access to culturally competent primary care, diagnostic screening, psychotherapy, and pharmacologic treatments, and retention in care in clinical community-based pediatric and young-adult medicine settings, are urgently needed to address the adverse mental health and substance dependence disorders in this population,” said Sari L. Reisner, Sc.D., of Boston Children’s Hospital and Harvard Medical School, and his associates.

They assessed mental health using brief structured diagnostic interviews with 298 young transgender women participating in an HIV-prevention study in Boston and Chicago during a 3-year period. The study participants, all aged 16-29 years (mean age, 23 years), had been assigned male sex at birth but self-identified as woman, female, transgender woman, transfemale, male-to-female, or other identity on the transfeminine spectrum. All reported participating in high-risk sexual activity. The study population was urban and ethnically diverse: 49.0% black, 12.4% Latina, 25.5% white, and 13.1% other race/ethnicity. Seventy-two percent reported ever using cross-sex hormones and 21% had undergone gender-reassignment surgery.

A total of 42% of these study participants had at least one psychiatric disorder, and 20% had two or more mental health diagnoses. The prevalence of lifetime major depressive disorder was 35%, suicidality within the preceding month was 20.2%, generalized anxiety disorder during the preceding 6 months was 8%, PTSD during the preceding 6 months was 10%, alcohol dependence during the preceding year was 11%, and substance dependence during the preceding year was 15%.

These findings suggest that stressors that are unique to gender transition, such as adverse processes in identity development, “may affect psychiatric health and well-being across adolescence and young adulthood,” the investigators said (JAMA Pediatr. 2016 March 21 doi: 10.1001/jamapediatrics.2016.0067).

“Pediatric, adolescent, or young-adult primary-care providers may be a first resource for families needing education and support and play a critical role in supporting transgender youth, including screening for psychosocial problems and health risks, referring for gender-specific mental health and medical care, and providing advocacy and support,” Dr. Reisner and his associates said.

They added that clinicians “should familiarize themselves with current international guidelines for the provision of clinical care to transgender young people, to best meet both medical and mental health needs of this at-risk population.”

This study was supported by the National Institute of Mental Health. Dr. Reisner and his associates reported having no relevant financial disclosures.

Young transgender women have a high prevalence of psychiatric disorders that is two to four times higher than that in the general population, according to a report published online March 21 in JAMA Pediatrics.

“Improving access to culturally competent primary care, diagnostic screening, psychotherapy, and pharmacologic treatments, and retention in care in clinical community-based pediatric and young-adult medicine settings, are urgently needed to address the adverse mental health and substance dependence disorders in this population,” said Sari L. Reisner, Sc.D., of Boston Children’s Hospital and Harvard Medical School, and his associates.

They assessed mental health using brief structured diagnostic interviews with 298 young transgender women participating in an HIV-prevention study in Boston and Chicago during a 3-year period. The study participants, all aged 16-29 years (mean age, 23 years), had been assigned male sex at birth but self-identified as woman, female, transgender woman, transfemale, male-to-female, or other identity on the transfeminine spectrum. All reported participating in high-risk sexual activity. The study population was urban and ethnically diverse: 49.0% black, 12.4% Latina, 25.5% white, and 13.1% other race/ethnicity. Seventy-two percent reported ever using cross-sex hormones and 21% had undergone gender-reassignment surgery.

A total of 42% of these study participants had at least one psychiatric disorder, and 20% had two or more mental health diagnoses. The prevalence of lifetime major depressive disorder was 35%, suicidality within the preceding month was 20.2%, generalized anxiety disorder during the preceding 6 months was 8%, PTSD during the preceding 6 months was 10%, alcohol dependence during the preceding year was 11%, and substance dependence during the preceding year was 15%.

These findings suggest that stressors that are unique to gender transition, such as adverse processes in identity development, “may affect psychiatric health and well-being across adolescence and young adulthood,” the investigators said (JAMA Pediatr. 2016 March 21 doi: 10.1001/jamapediatrics.2016.0067).

“Pediatric, adolescent, or young-adult primary-care providers may be a first resource for families needing education and support and play a critical role in supporting transgender youth, including screening for psychosocial problems and health risks, referring for gender-specific mental health and medical care, and providing advocacy and support,” Dr. Reisner and his associates said.

They added that clinicians “should familiarize themselves with current international guidelines for the provision of clinical care to transgender young people, to best meet both medical and mental health needs of this at-risk population.”

This study was supported by the National Institute of Mental Health. Dr. Reisner and his associates reported having no relevant financial disclosures.

Young transgender women have a high prevalence of psychiatric disorders that is two to four times higher than that in the general population, according to a report published online March 21 in JAMA Pediatrics.

“Improving access to culturally competent primary care, diagnostic screening, psychotherapy, and pharmacologic treatments, and retention in care in clinical community-based pediatric and young-adult medicine settings, are urgently needed to address the adverse mental health and substance dependence disorders in this population,” said Sari L. Reisner, Sc.D., of Boston Children’s Hospital and Harvard Medical School, and his associates.

They assessed mental health using brief structured diagnostic interviews with 298 young transgender women participating in an HIV-prevention study in Boston and Chicago during a 3-year period. The study participants, all aged 16-29 years (mean age, 23 years), had been assigned male sex at birth but self-identified as woman, female, transgender woman, transfemale, male-to-female, or other identity on the transfeminine spectrum. All reported participating in high-risk sexual activity. The study population was urban and ethnically diverse: 49.0% black, 12.4% Latina, 25.5% white, and 13.1% other race/ethnicity. Seventy-two percent reported ever using cross-sex hormones and 21% had undergone gender-reassignment surgery.

A total of 42% of these study participants had at least one psychiatric disorder, and 20% had two or more mental health diagnoses. The prevalence of lifetime major depressive disorder was 35%, suicidality within the preceding month was 20.2%, generalized anxiety disorder during the preceding 6 months was 8%, PTSD during the preceding 6 months was 10%, alcohol dependence during the preceding year was 11%, and substance dependence during the preceding year was 15%.

These findings suggest that stressors that are unique to gender transition, such as adverse processes in identity development, “may affect psychiatric health and well-being across adolescence and young adulthood,” the investigators said (JAMA Pediatr. 2016 March 21 doi: 10.1001/jamapediatrics.2016.0067).

“Pediatric, adolescent, or young-adult primary-care providers may be a first resource for families needing education and support and play a critical role in supporting transgender youth, including screening for psychosocial problems and health risks, referring for gender-specific mental health and medical care, and providing advocacy and support,” Dr. Reisner and his associates said.

They added that clinicians “should familiarize themselves with current international guidelines for the provision of clinical care to transgender young people, to best meet both medical and mental health needs of this at-risk population.”

This study was supported by the National Institute of Mental Health. Dr. Reisner and his associates reported having no relevant financial disclosures.

Placement of a pessary to support a short cervix failed to prevent preterm delivery, compared with expectant management, in an international open-label trial reported online March 16 in the New England Journal of Medicine.

Transvaginal placement of a silicone pessary around the cervix “is thought to support the cervix and change its direction toward the sacrum, thereby reducing the direct pressure from the uterine contents on the cervical canal.” However, two recent randomized trials of this treatment produced contradictory results, with one showing the device reducing the rate of spontaneous preterm delivery and the other showing it had no effect, reported Dr. Kypros H. Nicolaides of the Harris Birthright Research Center for Fetal Medicine, King’s College, London, and his colleagues.

©monkeybusinessimages/thinkstockphotos.com

They performed a randomized trial of women aged 16 years and older who had singleton pregnancies and who were found at routine ultrasound examination at 20-24 weeks’ gestation to have a cervical length of 25 mm or less. These study participants – enrolled during a 5-year period at 16 maternity hospitals in England, Slovenia, Portugal, Chile, Australia, Italy, Albania, Germany, and Belgium – were assigned to either placement of a cervical pessary or expectant management and followed every 4 weeks until delivery. The analysis included 465 women in the pessary group and 467 women in the control group.

Women who had a very short cervix (15 mm or less) were also given intravaginal progesterone capsules to use nightly.

The primary outcome measure – spontaneous delivery before 34 weeks’ gestation – occurred in 55 women (12.0%) who received pessaries and 50 (10.8%) in the control group. This outcome remained similar between the two study groups when the data were adjusted to control for treatment center and for the patients’ cervical length, obstetric history, progesterone use, and antibiotic treatment.

Secondary outcomes of perinatal death, adverse neonatal events, and need for special neonatal care also did not differ significantly between women who received a pessary and those who did not, the researchers reported (N Engl J Med. 2016;374:1044-52). Both the primary and secondary outcomes were unchanged in a series of post-hoc subgroup analyses.

Women who received a pessary reported higher rates of new or increased vaginal discharge (46.8% vs. 13.8%) and pelvic discomfort (11.4% vs. 3.4%) during follow-up visits. Pessaries were removed before 34 weeks’ in 114 women (24.5%), usually due to iatrogenic delivery, preterm labor, or premature rupture of the membranes. But 47 women requested pessary removal because of discomfort, vaginal discharge, or vaginal bleeding.

This study was supported by the Fetal Medicine Foundation. Dr. Nicolaides and his colleagues reported having no relevant financial disclosures.

Placement of a pessary to support a short cervix failed to prevent preterm delivery, compared with expectant management, in an international open-label trial reported online March 16 in the New England Journal of Medicine.

Transvaginal placement of a silicone pessary around the cervix “is thought to support the cervix and change its direction toward the sacrum, thereby reducing the direct pressure from the uterine contents on the cervical canal.” However, two recent randomized trials of this treatment produced contradictory results, with one showing the device reducing the rate of spontaneous preterm delivery and the other showing it had no effect, reported Dr. Kypros H. Nicolaides of the Harris Birthright Research Center for Fetal Medicine, King’s College, London, and his colleagues.

©monkeybusinessimages/thinkstockphotos.com

They performed a randomized trial of women aged 16 years and older who had singleton pregnancies and who were found at routine ultrasound examination at 20-24 weeks’ gestation to have a cervical length of 25 mm or less. These study participants – enrolled during a 5-year period at 16 maternity hospitals in England, Slovenia, Portugal, Chile, Australia, Italy, Albania, Germany, and Belgium – were assigned to either placement of a cervical pessary or expectant management and followed every 4 weeks until delivery. The analysis included 465 women in the pessary group and 467 women in the control group.

Women who had a very short cervix (15 mm or less) were also given intravaginal progesterone capsules to use nightly.

The primary outcome measure – spontaneous delivery before 34 weeks’ gestation – occurred in 55 women (12.0%) who received pessaries and 50 (10.8%) in the control group. This outcome remained similar between the two study groups when the data were adjusted to control for treatment center and for the patients’ cervical length, obstetric history, progesterone use, and antibiotic treatment.

Secondary outcomes of perinatal death, adverse neonatal events, and need for special neonatal care also did not differ significantly between women who received a pessary and those who did not, the researchers reported (N Engl J Med. 2016;374:1044-52). Both the primary and secondary outcomes were unchanged in a series of post-hoc subgroup analyses.

Women who received a pessary reported higher rates of new or increased vaginal discharge (46.8% vs. 13.8%) and pelvic discomfort (11.4% vs. 3.4%) during follow-up visits. Pessaries were removed before 34 weeks’ in 114 women (24.5%), usually due to iatrogenic delivery, preterm labor, or premature rupture of the membranes. But 47 women requested pessary removal because of discomfort, vaginal discharge, or vaginal bleeding.

This study was supported by the Fetal Medicine Foundation. Dr. Nicolaides and his colleagues reported having no relevant financial disclosures.

Placement of a pessary to support a short cervix failed to prevent preterm delivery, compared with expectant management, in an international open-label trial reported online March 16 in the New England Journal of Medicine.

Transvaginal placement of a silicone pessary around the cervix “is thought to support the cervix and change its direction toward the sacrum, thereby reducing the direct pressure from the uterine contents on the cervical canal.” However, two recent randomized trials of this treatment produced contradictory results, with one showing the device reducing the rate of spontaneous preterm delivery and the other showing it had no effect, reported Dr. Kypros H. Nicolaides of the Harris Birthright Research Center for Fetal Medicine, King’s College, London, and his colleagues.

©monkeybusinessimages/thinkstockphotos.com

They performed a randomized trial of women aged 16 years and older who had singleton pregnancies and who were found at routine ultrasound examination at 20-24 weeks’ gestation to have a cervical length of 25 mm or less. These study participants – enrolled during a 5-year period at 16 maternity hospitals in England, Slovenia, Portugal, Chile, Australia, Italy, Albania, Germany, and Belgium – were assigned to either placement of a cervical pessary or expectant management and followed every 4 weeks until delivery. The analysis included 465 women in the pessary group and 467 women in the control group.

Women who had a very short cervix (15 mm or less) were also given intravaginal progesterone capsules to use nightly.

The primary outcome measure – spontaneous delivery before 34 weeks’ gestation – occurred in 55 women (12.0%) who received pessaries and 50 (10.8%) in the control group. This outcome remained similar between the two study groups when the data were adjusted to control for treatment center and for the patients’ cervical length, obstetric history, progesterone use, and antibiotic treatment.

Secondary outcomes of perinatal death, adverse neonatal events, and need for special neonatal care also did not differ significantly between women who received a pessary and those who did not, the researchers reported (N Engl J Med. 2016;374:1044-52). Both the primary and secondary outcomes were unchanged in a series of post-hoc subgroup analyses.

Women who received a pessary reported higher rates of new or increased vaginal discharge (46.8% vs. 13.8%) and pelvic discomfort (11.4% vs. 3.4%) during follow-up visits. Pessaries were removed before 34 weeks’ in 114 women (24.5%), usually due to iatrogenic delivery, preterm labor, or premature rupture of the membranes. But 47 women requested pessary removal because of discomfort, vaginal discharge, or vaginal bleeding.

This study was supported by the Fetal Medicine Foundation. Dr. Nicolaides and his colleagues reported having no relevant financial disclosures.

The closer that older adults come to meeting the American Heart Association’s “ideal” targets for seven factors that determine cardiovascular health, the lower their risk for cognitive decline, according to a report published online March 16 in Journal of the American Heart Association.

A secondary analysis of data from a prospective population-based cohort study of stroke risk demonstrated that better alignment with the AHA’s “Life’s Simple 7” cardiovascular health metrics correlated with less decline in mental processing speed, and, to a lesser extent, in executive function and episodic memory. “The results of this study suggest that achievement of the AHA’s ideal cardiovascular health metrics may have benefits for brain health, in addition to preventing strokes and myocardial infarctions ... underscoring the importance of public health initiatives aimed to better control these seven factors,” said Hannah Gardener, Sc.D., of the department of neurology, University of Miami, and her associates.

The AHA recently defined ideal target levels for seven modifiable cardiovascular (CV) risk factors: smoking status, body mass index, physical activity level, diet, blood pressure, total cholesterol level, and fasting glucose level. Meeting or closely approaching these ideals has already been linked to a decreased risk of stroke and MI. To examine a possible association with brain health, Dr. Gardener and her colleagues assessed these seven metrics in an ethnically diverse cohort of 722 participants aged 50 years and older in the Northern Manhattan Study who underwent serial comprehensive neuropsychological testing including brain MRI.

Of the total cohort, 3% had zero ideal factors, 15% had one factor, 33% had two factors, 30% had three factors, 14% had four factors, 14% had five factors, 1% had six factors, and none had all seven factors.

“An increasing number of ideal cardiovascular health factors was positively associated with processing speed,” and the association was particularly strong for three of the factors: ideal body mass index, lack of smoking, and ideal fasting glucose level. This association persisted when the data were adjusted to account for MRI markers of subclinical vascular damage, such as abnormalities in white matter volume, brain atrophy, and previous infarctions. A similar but less strong association was seen between an increasing number of ideal cardiovascular health factors and performance on measures of episodic memory and executive function.

These seven CV factors also were associated with less decline over time in these three areas of cognitive function. In contrast, the CV factors showed no association with measures of semantic memory, the investigators said (J Am Heart Assoc. 2016 Mar 16).

The associations remained unchanged in sensitivity analyses that controlled for the presence and severity of depression.

“The results of our study add to a growing body of literature suggesting the effects of smoking and blood glucose levels on cognitive health in particular,” and support the role of vascular damage and metabolic processes in the etiology of cognitive aging and dementia, they added.

The closer that older adults come to meeting the American Heart Association’s “ideal” targets for seven factors that determine cardiovascular health, the lower their risk for cognitive decline, according to a report published online March 16 in Journal of the American Heart Association.

A secondary analysis of data from a prospective population-based cohort study of stroke risk demonstrated that better alignment with the AHA’s “Life’s Simple 7” cardiovascular health metrics correlated with less decline in mental processing speed, and, to a lesser extent, in executive function and episodic memory. “The results of this study suggest that achievement of the AHA’s ideal cardiovascular health metrics may have benefits for brain health, in addition to preventing strokes and myocardial infarctions ... underscoring the importance of public health initiatives aimed to better control these seven factors,” said Hannah Gardener, Sc.D., of the department of neurology, University of Miami, and her associates.

The AHA recently defined ideal target levels for seven modifiable cardiovascular (CV) risk factors: smoking status, body mass index, physical activity level, diet, blood pressure, total cholesterol level, and fasting glucose level. Meeting or closely approaching these ideals has already been linked to a decreased risk of stroke and MI. To examine a possible association with brain health, Dr. Gardener and her colleagues assessed these seven metrics in an ethnically diverse cohort of 722 participants aged 50 years and older in the Northern Manhattan Study who underwent serial comprehensive neuropsychological testing including brain MRI.

Of the total cohort, 3% had zero ideal factors, 15% had one factor, 33% had two factors, 30% had three factors, 14% had four factors, 14% had five factors, 1% had six factors, and none had all seven factors.

“An increasing number of ideal cardiovascular health factors was positively associated with processing speed,” and the association was particularly strong for three of the factors: ideal body mass index, lack of smoking, and ideal fasting glucose level. This association persisted when the data were adjusted to account for MRI markers of subclinical vascular damage, such as abnormalities in white matter volume, brain atrophy, and previous infarctions. A similar but less strong association was seen between an increasing number of ideal cardiovascular health factors and performance on measures of episodic memory and executive function.

These seven CV factors also were associated with less decline over time in these three areas of cognitive function. In contrast, the CV factors showed no association with measures of semantic memory, the investigators said (J Am Heart Assoc. 2016 Mar 16).

The associations remained unchanged in sensitivity analyses that controlled for the presence and severity of depression.

“The results of our study add to a growing body of literature suggesting the effects of smoking and blood glucose levels on cognitive health in particular,” and support the role of vascular damage and metabolic processes in the etiology of cognitive aging and dementia, they added.

The closer that older adults come to meeting the American Heart Association’s “ideal” targets for seven factors that determine cardiovascular health, the lower their risk for cognitive decline, according to a report published online March 16 in Journal of the American Heart Association.

A secondary analysis of data from a prospective population-based cohort study of stroke risk demonstrated that better alignment with the AHA’s “Life’s Simple 7” cardiovascular health metrics correlated with less decline in mental processing speed, and, to a lesser extent, in executive function and episodic memory. “The results of this study suggest that achievement of the AHA’s ideal cardiovascular health metrics may have benefits for brain health, in addition to preventing strokes and myocardial infarctions ... underscoring the importance of public health initiatives aimed to better control these seven factors,” said Hannah Gardener, Sc.D., of the department of neurology, University of Miami, and her associates.

The AHA recently defined ideal target levels for seven modifiable cardiovascular (CV) risk factors: smoking status, body mass index, physical activity level, diet, blood pressure, total cholesterol level, and fasting glucose level. Meeting or closely approaching these ideals has already been linked to a decreased risk of stroke and MI. To examine a possible association with brain health, Dr. Gardener and her colleagues assessed these seven metrics in an ethnically diverse cohort of 722 participants aged 50 years and older in the Northern Manhattan Study who underwent serial comprehensive neuropsychological testing including brain MRI.

Of the total cohort, 3% had zero ideal factors, 15% had one factor, 33% had two factors, 30% had three factors, 14% had four factors, 14% had five factors, 1% had six factors, and none had all seven factors.

“An increasing number of ideal cardiovascular health factors was positively associated with processing speed,” and the association was particularly strong for three of the factors: ideal body mass index, lack of smoking, and ideal fasting glucose level. This association persisted when the data were adjusted to account for MRI markers of subclinical vascular damage, such as abnormalities in white matter volume, brain atrophy, and previous infarctions. A similar but less strong association was seen between an increasing number of ideal cardiovascular health factors and performance on measures of episodic memory and executive function.

These seven CV factors also were associated with less decline over time in these three areas of cognitive function. In contrast, the CV factors showed no association with measures of semantic memory, the investigators said (J Am Heart Assoc. 2016 Mar 16).

The associations remained unchanged in sensitivity analyses that controlled for the presence and severity of depression.

“The results of our study add to a growing body of literature suggesting the effects of smoking and blood glucose levels on cognitive health in particular,” and support the role of vascular damage and metabolic processes in the etiology of cognitive aging and dementia, they added.