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Adding biomarkers beats NICE guidelines for detecting preeclampsia
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
Key clinical point: Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines only detects around one-third of all preeclampsia cases, but the addition of biomarkers can improve this significantly.
Major finding: The NICE guidelines detected 30.4% of cases of preeclampsia, while a Bayes’ theorem-based method using maternal risk factors and biomarkers detected 42.5%.
Data source: A prospective multicenter study of 16,747 singleton pregnancies.
Disclosures: The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
Source: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
mainbar
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.
The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
High-normal TSH linked to unexplained infertility
CHICAGO – Levels of thyroid stimulating hormone were significantly higher in women with unexplained infertility than in a cohort whose partners had severe male factor infertility, though TSH levels still fell within the reference range.
For women with unexplained infertility, thyroid stimulating hormone (TSH) averaged 1.95 mIU/mL (95% confidence interval, 1.54-2.61), compared with 1.66 mIU/mL for the group of women with severe male factor infertility, such as severe oligospermia or azoospermia (95% CI, 1.25-2.17; P = .003).
“We found, very interestingly, that in the unexplained group, TSH was higher in those women, compared with women whose partners had severe male factor infertility,” suggesting that , the study’s first author, Lindsay T. Fourman, MD, said in an interview at the annual meeting of the Endocrine Society.
In terms of TSH levels, “clearly, the cutoff of the upper limit of the normal range is controversial,” said Dr. Fourman. “Some studies have shown that 95% of the population has a TSH of less than 2.5.”
However, the numbers that guide treatment for hypothyroidism are different. “We use a cutoff, generally, of 4 or 5, but maybe that cutoff should be 2.5, and maybe that’s significant for some people,” Dr. Fourman said.
“Current guidelines do not recommend treatment of subclinical hypothyroidism among auto-antibody negative women attempting to conceive naturally,” wrote Dr. Fourman and her collaborators in the poster presenting their finding.
Twice as many women in the group with unexplained infertility had TSH levels in the upper half of the normal range – above 2.5 mIU/mL – than in the male factor infertility group, “again, suggesting this association with TSH and unexplained infertility,” Dr. Fourman said. The thyroid axis is known to play a role in oocyte development. Of women with unexplained infertility, 26.9% had a TSH above 5 mIU/mL, compared with 13.5% of those with severe male factor infertility (P less than .05).
The chart review of records from 187 women with unexplained fertility and 52 women whose partners had severe male factor infertility included women aged 18-39. The unexplained cohort included women for whom all causes of infertility were excluded “in the setting of a very thorough workup – and that would include any ovulatory issues, male factor issues, and by definition, these women had to have a normal FSH, TSH and prolactin,” said Dr. Fourman, an endocrine fellow at Massachusetts General Hospital, Boston.
Control patients were those who had TSH and prolactin levels available and whose partners were being seen for severe male factor infertility, meaning that their partner had severe oligospermia or azoospermia.
Dr. Fourman acknowledged that she and her and her collaborators couldn’t exclude some female factor infertility among the control group. “That is an assumption, but it’s an assumption that would bias us to the null,” strengthening the study’s findings.
Clinical characteristics were similar between study groups, though women with unexplained infertility were slightly older than those with severe male factor infertility (mean 31.5 years versus 30.1 years, P = .01); they also had slightly lower body mass indices (median 23 versus 24.4 kg/m2; P less than .04).
No association was found between prolactin levels, “which suggests that prolactin may not contribute to unexplained infertility in these women,” Dr. Fourman said.
The investigators were able to control for such potentially confounding variables as age, tobacco use, BMI; they excluded from analysis women who had positive thyroid peroxidase antibodies.
“This is very interesting, because it really raises the question of whether we should be treating TSH, even to the lower half of the normal range, to see if that can improve outcomes,” she said. “We are looking for modifiable things that we can treat to try to improve fertility, so if we can identify some cause – like a hormonal cause – we may be able to improve conception outcomes and reduce the need for invasive treatment.”
Based in part on the strength of these findings, Dr. Fourman said she and her collaborators are planning a prospective study to see whether treating women with infertility to achieve a TSH of less than 2.5 can speed time to conception and reduce the need for invasive infertility treatment.
Dr. Fourman reported no conflicts of interest and no external sources of funding.
SOURCE: Fourman, L, et al. ENDO 2018, Abstract SAT-288.
CHICAGO – Levels of thyroid stimulating hormone were significantly higher in women with unexplained infertility than in a cohort whose partners had severe male factor infertility, though TSH levels still fell within the reference range.
For women with unexplained infertility, thyroid stimulating hormone (TSH) averaged 1.95 mIU/mL (95% confidence interval, 1.54-2.61), compared with 1.66 mIU/mL for the group of women with severe male factor infertility, such as severe oligospermia or azoospermia (95% CI, 1.25-2.17; P = .003).
“We found, very interestingly, that in the unexplained group, TSH was higher in those women, compared with women whose partners had severe male factor infertility,” suggesting that , the study’s first author, Lindsay T. Fourman, MD, said in an interview at the annual meeting of the Endocrine Society.
In terms of TSH levels, “clearly, the cutoff of the upper limit of the normal range is controversial,” said Dr. Fourman. “Some studies have shown that 95% of the population has a TSH of less than 2.5.”
However, the numbers that guide treatment for hypothyroidism are different. “We use a cutoff, generally, of 4 or 5, but maybe that cutoff should be 2.5, and maybe that’s significant for some people,” Dr. Fourman said.
“Current guidelines do not recommend treatment of subclinical hypothyroidism among auto-antibody negative women attempting to conceive naturally,” wrote Dr. Fourman and her collaborators in the poster presenting their finding.
Twice as many women in the group with unexplained infertility had TSH levels in the upper half of the normal range – above 2.5 mIU/mL – than in the male factor infertility group, “again, suggesting this association with TSH and unexplained infertility,” Dr. Fourman said. The thyroid axis is known to play a role in oocyte development. Of women with unexplained infertility, 26.9% had a TSH above 5 mIU/mL, compared with 13.5% of those with severe male factor infertility (P less than .05).
The chart review of records from 187 women with unexplained fertility and 52 women whose partners had severe male factor infertility included women aged 18-39. The unexplained cohort included women for whom all causes of infertility were excluded “in the setting of a very thorough workup – and that would include any ovulatory issues, male factor issues, and by definition, these women had to have a normal FSH, TSH and prolactin,” said Dr. Fourman, an endocrine fellow at Massachusetts General Hospital, Boston.
Control patients were those who had TSH and prolactin levels available and whose partners were being seen for severe male factor infertility, meaning that their partner had severe oligospermia or azoospermia.
Dr. Fourman acknowledged that she and her and her collaborators couldn’t exclude some female factor infertility among the control group. “That is an assumption, but it’s an assumption that would bias us to the null,” strengthening the study’s findings.
Clinical characteristics were similar between study groups, though women with unexplained infertility were slightly older than those with severe male factor infertility (mean 31.5 years versus 30.1 years, P = .01); they also had slightly lower body mass indices (median 23 versus 24.4 kg/m2; P less than .04).
No association was found between prolactin levels, “which suggests that prolactin may not contribute to unexplained infertility in these women,” Dr. Fourman said.
The investigators were able to control for such potentially confounding variables as age, tobacco use, BMI; they excluded from analysis women who had positive thyroid peroxidase antibodies.
“This is very interesting, because it really raises the question of whether we should be treating TSH, even to the lower half of the normal range, to see if that can improve outcomes,” she said. “We are looking for modifiable things that we can treat to try to improve fertility, so if we can identify some cause – like a hormonal cause – we may be able to improve conception outcomes and reduce the need for invasive treatment.”
Based in part on the strength of these findings, Dr. Fourman said she and her collaborators are planning a prospective study to see whether treating women with infertility to achieve a TSH of less than 2.5 can speed time to conception and reduce the need for invasive infertility treatment.
Dr. Fourman reported no conflicts of interest and no external sources of funding.
SOURCE: Fourman, L, et al. ENDO 2018, Abstract SAT-288.
CHICAGO – Levels of thyroid stimulating hormone were significantly higher in women with unexplained infertility than in a cohort whose partners had severe male factor infertility, though TSH levels still fell within the reference range.
For women with unexplained infertility, thyroid stimulating hormone (TSH) averaged 1.95 mIU/mL (95% confidence interval, 1.54-2.61), compared with 1.66 mIU/mL for the group of women with severe male factor infertility, such as severe oligospermia or azoospermia (95% CI, 1.25-2.17; P = .003).
“We found, very interestingly, that in the unexplained group, TSH was higher in those women, compared with women whose partners had severe male factor infertility,” suggesting that , the study’s first author, Lindsay T. Fourman, MD, said in an interview at the annual meeting of the Endocrine Society.
In terms of TSH levels, “clearly, the cutoff of the upper limit of the normal range is controversial,” said Dr. Fourman. “Some studies have shown that 95% of the population has a TSH of less than 2.5.”
However, the numbers that guide treatment for hypothyroidism are different. “We use a cutoff, generally, of 4 or 5, but maybe that cutoff should be 2.5, and maybe that’s significant for some people,” Dr. Fourman said.
“Current guidelines do not recommend treatment of subclinical hypothyroidism among auto-antibody negative women attempting to conceive naturally,” wrote Dr. Fourman and her collaborators in the poster presenting their finding.
Twice as many women in the group with unexplained infertility had TSH levels in the upper half of the normal range – above 2.5 mIU/mL – than in the male factor infertility group, “again, suggesting this association with TSH and unexplained infertility,” Dr. Fourman said. The thyroid axis is known to play a role in oocyte development. Of women with unexplained infertility, 26.9% had a TSH above 5 mIU/mL, compared with 13.5% of those with severe male factor infertility (P less than .05).
The chart review of records from 187 women with unexplained fertility and 52 women whose partners had severe male factor infertility included women aged 18-39. The unexplained cohort included women for whom all causes of infertility were excluded “in the setting of a very thorough workup – and that would include any ovulatory issues, male factor issues, and by definition, these women had to have a normal FSH, TSH and prolactin,” said Dr. Fourman, an endocrine fellow at Massachusetts General Hospital, Boston.
Control patients were those who had TSH and prolactin levels available and whose partners were being seen for severe male factor infertility, meaning that their partner had severe oligospermia or azoospermia.
Dr. Fourman acknowledged that she and her and her collaborators couldn’t exclude some female factor infertility among the control group. “That is an assumption, but it’s an assumption that would bias us to the null,” strengthening the study’s findings.
Clinical characteristics were similar between study groups, though women with unexplained infertility were slightly older than those with severe male factor infertility (mean 31.5 years versus 30.1 years, P = .01); they also had slightly lower body mass indices (median 23 versus 24.4 kg/m2; P less than .04).
No association was found between prolactin levels, “which suggests that prolactin may not contribute to unexplained infertility in these women,” Dr. Fourman said.
The investigators were able to control for such potentially confounding variables as age, tobacco use, BMI; they excluded from analysis women who had positive thyroid peroxidase antibodies.
“This is very interesting, because it really raises the question of whether we should be treating TSH, even to the lower half of the normal range, to see if that can improve outcomes,” she said. “We are looking for modifiable things that we can treat to try to improve fertility, so if we can identify some cause – like a hormonal cause – we may be able to improve conception outcomes and reduce the need for invasive treatment.”
Based in part on the strength of these findings, Dr. Fourman said she and her collaborators are planning a prospective study to see whether treating women with infertility to achieve a TSH of less than 2.5 can speed time to conception and reduce the need for invasive infertility treatment.
Dr. Fourman reported no conflicts of interest and no external sources of funding.
SOURCE: Fourman, L, et al. ENDO 2018, Abstract SAT-288.
REPORTING FROM ENDO 2018
Three regular meals a day is best in T2DM
CHICAGO – Spreading calories out over three regular meals a day, instead of six small ones, helps patients with type 2 diabetes lose weight and better control their blood glucose, especially when breakfast is the main meal of the day, according to Israeli investigators.
Too often, obese type 2 patients end up on a treadmill of ever-increasing insulin doses that lead, in turn, to more weight gain and still more insulin, plus greater risk of diabetic complications. “To break this vicious cycle, we need to better control diabetes with less insulin,” said lead investigator Daniela Jakubowicz, MD, an endocrinologist at the Wolfson Medical Center at Tel Aviv University.
The team had a hunch that meal-timing would help, so they randomized 19 obese, uncontrolled type 2 patients to three meals a day, and 18 to six meals. The overall calories were the same in each arm: 1,500-1,800 per day.
Those in the three-meal (3m) group took 50% of their calories at breakfast, mostly from carbohydrates and protein, and consumed by 9:30 a.m. One-third of their calories were consumed at lunch, and the final 17% at dinner, where carbohydrates were not allowed. Between-meal snacking on vegetables was allowed. The six-meal (6m) group took 20%, 25%, and 25% of their calories at breakfast, lunch, and dinner, plus three snacks each consisting of 10% of their daily caloric intake. The study included a few more men than women, and insulin was titrated biweekly in the two groups as needed.
The groups were statistically identical at baseline, with a mean age of about 70 years, a 20-year or so history of type 2 diabetes, and a mean body mass index (BMI) of just under 33 kg/m2. However, at the end of 3 months, the 3m group was doing much better.They had lost a mean of 5.4 kg at that point and reduced their BMI by a mean of 1.9 kg/m2 and their HbA1c 1.2%. The 6m group, meanwhile, gained a mean of 0.26 kg, increased their BMI 0.1 kg/m2, and dropped their HbA1c only 0.2%. Both groups started with a mean HbA1c of around 8%.
Hunger and craving scores improved in the 3m group, as well, and their total daily insulin dose dropped 27 units from a baseline of 74 units; 6m subjects went up 5 units/day, from a baseline of 71 units. The findings were all statistically significant.
In short, the 3m is “more effective than the traditional diet with six small meals evenly distributed along the day, for weight loss, overall glycemia, HbA1c, appetite, and for the reduction of insulin requirements. Therefore, the three-meal schedule with a high-energy breakfast “should be a strategy to improve diabetes control and outcome,” Dr. Jakubowicz said at the annual meeting of the Endocrine Society.
The findings caught the attention of her audience. One endocrinologist said that “patients always ask me about doing six small meals a day.”
Most of the mean blood glucose reduction found in the 3m group happened after only 14 days on the diet, suggesting an improvement in hepatic insulin sensitivity. There was no correlation between glucose levels and weight; the beneficial effects of the 3m diet appeared independent of weight loss.
Those benefits instead might attributable to effects on “clock genes,” which control the circadian oscillation of gene expression. The investigators are looking into the matter further. .
The funding source was not reported. Dr. Jakubowicz, author of “The Big Breakfast Diet” (Workman Publishing Co., 2009), had no other disclosures. The other investigators had no disclosures.
SOURCE: Jakubowicz D et al. ENDO 2018, Abstract OR05-2.
CHICAGO – Spreading calories out over three regular meals a day, instead of six small ones, helps patients with type 2 diabetes lose weight and better control their blood glucose, especially when breakfast is the main meal of the day, according to Israeli investigators.
Too often, obese type 2 patients end up on a treadmill of ever-increasing insulin doses that lead, in turn, to more weight gain and still more insulin, plus greater risk of diabetic complications. “To break this vicious cycle, we need to better control diabetes with less insulin,” said lead investigator Daniela Jakubowicz, MD, an endocrinologist at the Wolfson Medical Center at Tel Aviv University.
The team had a hunch that meal-timing would help, so they randomized 19 obese, uncontrolled type 2 patients to three meals a day, and 18 to six meals. The overall calories were the same in each arm: 1,500-1,800 per day.
Those in the three-meal (3m) group took 50% of their calories at breakfast, mostly from carbohydrates and protein, and consumed by 9:30 a.m. One-third of their calories were consumed at lunch, and the final 17% at dinner, where carbohydrates were not allowed. Between-meal snacking on vegetables was allowed. The six-meal (6m) group took 20%, 25%, and 25% of their calories at breakfast, lunch, and dinner, plus three snacks each consisting of 10% of their daily caloric intake. The study included a few more men than women, and insulin was titrated biweekly in the two groups as needed.
The groups were statistically identical at baseline, with a mean age of about 70 years, a 20-year or so history of type 2 diabetes, and a mean body mass index (BMI) of just under 33 kg/m2. However, at the end of 3 months, the 3m group was doing much better.They had lost a mean of 5.4 kg at that point and reduced their BMI by a mean of 1.9 kg/m2 and their HbA1c 1.2%. The 6m group, meanwhile, gained a mean of 0.26 kg, increased their BMI 0.1 kg/m2, and dropped their HbA1c only 0.2%. Both groups started with a mean HbA1c of around 8%.
Hunger and craving scores improved in the 3m group, as well, and their total daily insulin dose dropped 27 units from a baseline of 74 units; 6m subjects went up 5 units/day, from a baseline of 71 units. The findings were all statistically significant.
In short, the 3m is “more effective than the traditional diet with six small meals evenly distributed along the day, for weight loss, overall glycemia, HbA1c, appetite, and for the reduction of insulin requirements. Therefore, the three-meal schedule with a high-energy breakfast “should be a strategy to improve diabetes control and outcome,” Dr. Jakubowicz said at the annual meeting of the Endocrine Society.
The findings caught the attention of her audience. One endocrinologist said that “patients always ask me about doing six small meals a day.”
Most of the mean blood glucose reduction found in the 3m group happened after only 14 days on the diet, suggesting an improvement in hepatic insulin sensitivity. There was no correlation between glucose levels and weight; the beneficial effects of the 3m diet appeared independent of weight loss.
Those benefits instead might attributable to effects on “clock genes,” which control the circadian oscillation of gene expression. The investigators are looking into the matter further. .
The funding source was not reported. Dr. Jakubowicz, author of “The Big Breakfast Diet” (Workman Publishing Co., 2009), had no other disclosures. The other investigators had no disclosures.
SOURCE: Jakubowicz D et al. ENDO 2018, Abstract OR05-2.
CHICAGO – Spreading calories out over three regular meals a day, instead of six small ones, helps patients with type 2 diabetes lose weight and better control their blood glucose, especially when breakfast is the main meal of the day, according to Israeli investigators.
Too often, obese type 2 patients end up on a treadmill of ever-increasing insulin doses that lead, in turn, to more weight gain and still more insulin, plus greater risk of diabetic complications. “To break this vicious cycle, we need to better control diabetes with less insulin,” said lead investigator Daniela Jakubowicz, MD, an endocrinologist at the Wolfson Medical Center at Tel Aviv University.
The team had a hunch that meal-timing would help, so they randomized 19 obese, uncontrolled type 2 patients to three meals a day, and 18 to six meals. The overall calories were the same in each arm: 1,500-1,800 per day.
Those in the three-meal (3m) group took 50% of their calories at breakfast, mostly from carbohydrates and protein, and consumed by 9:30 a.m. One-third of their calories were consumed at lunch, and the final 17% at dinner, where carbohydrates were not allowed. Between-meal snacking on vegetables was allowed. The six-meal (6m) group took 20%, 25%, and 25% of their calories at breakfast, lunch, and dinner, plus three snacks each consisting of 10% of their daily caloric intake. The study included a few more men than women, and insulin was titrated biweekly in the two groups as needed.
The groups were statistically identical at baseline, with a mean age of about 70 years, a 20-year or so history of type 2 diabetes, and a mean body mass index (BMI) of just under 33 kg/m2. However, at the end of 3 months, the 3m group was doing much better.They had lost a mean of 5.4 kg at that point and reduced their BMI by a mean of 1.9 kg/m2 and their HbA1c 1.2%. The 6m group, meanwhile, gained a mean of 0.26 kg, increased their BMI 0.1 kg/m2, and dropped their HbA1c only 0.2%. Both groups started with a mean HbA1c of around 8%.
Hunger and craving scores improved in the 3m group, as well, and their total daily insulin dose dropped 27 units from a baseline of 74 units; 6m subjects went up 5 units/day, from a baseline of 71 units. The findings were all statistically significant.
In short, the 3m is “more effective than the traditional diet with six small meals evenly distributed along the day, for weight loss, overall glycemia, HbA1c, appetite, and for the reduction of insulin requirements. Therefore, the three-meal schedule with a high-energy breakfast “should be a strategy to improve diabetes control and outcome,” Dr. Jakubowicz said at the annual meeting of the Endocrine Society.
The findings caught the attention of her audience. One endocrinologist said that “patients always ask me about doing six small meals a day.”
Most of the mean blood glucose reduction found in the 3m group happened after only 14 days on the diet, suggesting an improvement in hepatic insulin sensitivity. There was no correlation between glucose levels and weight; the beneficial effects of the 3m diet appeared independent of weight loss.
Those benefits instead might attributable to effects on “clock genes,” which control the circadian oscillation of gene expression. The investigators are looking into the matter further. .
The funding source was not reported. Dr. Jakubowicz, author of “The Big Breakfast Diet” (Workman Publishing Co., 2009), had no other disclosures. The other investigators had no disclosures.
SOURCE: Jakubowicz D et al. ENDO 2018, Abstract OR05-2.
REPORTING FROM ENDO 2018
Key clinical point: Spreading calories out over three regular meals a day, instead of six small ones, helps patients with type 2 diabetes lose weight and better control their blood glucose, especially when breakfast is the main meal of the day.
Major finding: The total daily insulin dose dropped 27 units from a baseline of 74 units among patients assigned to get their calories at three regular meals; among subjects who had them spread out over six meals, the daily insulin dose increased 5 units/day, from a baseline of 71 units.
Study details: Randomized trial with 37 people with type 2 diabetes.
Disclosures: The funding source was not reported. Dr. Jakubowicz, author of “The Big Breakfast Diet” (Workman Publishing Co., 2009), had no other disclosures. The other investigators had no disclosures.
Source: Jakubowicz D et al. ENDO 2018, Abstract OR05-2.
Dose-escalated radiation therapy brings mixed results in prostate cancer
Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.
The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.
Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.
“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.
Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.
Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.
In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.
With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).
Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.
Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.
“,” Dr. Michalski and his associates wrote.
Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.
SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.
Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.
The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.
Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.
“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.
Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.
Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.
In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.
With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).
Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.
Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.
“,” Dr. Michalski and his associates wrote.
Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.
SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.
Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.
The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.
Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.
“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.
Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.
Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.
In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.
With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).
Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.
Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.
“,” Dr. Michalski and his associates wrote.
Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.
SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.
FROM JAMA ONCOLOGY
Key clinical point: Despite reducing the need for subsequent therapy, dose-escalated radiation therapy for intermediate-risk prostate cancer did not improve overall survival.
Major finding: Eight-year overall survival rates were 76% for dose-escalated radiation therapy, compared with 75% for standard radiation therapy (P = 0.98).
Study details: The randomized NRG Oncology/RTOG 0126 clinical trial including 1,532 patients enrolled between March 2002 and August 2008 at one of 104 North American sites.
Disclosures: Dr. Michalsky reported no conflicts of interest. The study authors disclosed conflicts tied to several companies, including ViewRay, Augmenix, Sanofi, AstraZeneca, and AbbVie.
Source: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.
Surgery indicates higher survival with adrenal cortical carcinoma
CHICAGO –
These findings, uncovered using the largest cancer registry in the United States, will help give physicians insight into what the best course of action is for treating their patients, according to presenters.
“Surgical resection of the primary tumor improved survival in all stages of disease, whereas adjuvant therapy with chemotherapy or radiation improved overall survival only in stage IVpatients,” said Sri Harsha Tella, MD, endocrinologist at the University of South Carolina, Columbia. “These results may help the prognostication of patients in treatment decision making.”
Investigators conducted a retrospective study of 3,185 pathologically confirmed cases of ACC, registered into the National Cancer Database between 2004 and 2015.
Patients were mostly women with an average age of 55 years old and private insurance, with a nearly even split of patients with stage I-III (26%) and stage IV ACC (24%). Nearly three-quarters of those studied chose to have surgery, of which 31% chose open resection.
Patients with stage I-III ACC had a significant median survival rate of 63 months, compared with those who did not have surgery who had an average survival of 8 months.
In patients with stage IV ACC, surgery lengthened overall survival to 19 months, compared with 6 months for those without surgery, according to Dr. Tella and fellow investigators.
While surgery did have a greater positive effect on patients’ live spans across all stages, the impact of chemotherapy and radiation was significant only among stage IV patients who had complete surgery.
Those in the stage IV group who were given post-surgery adjuvant chemotherapy were likely to live an average of nearly 9 more months than did those who did not have chemotherapy after radiation (22 vs. 13), while those given radiation therapy saw an increase in survival by 19 months (29 vs. 10). These increases did not affect stage I-III patients, who had a similar rate of survival regardless of additional therapies after their surgery (24 vs. 25 months).
One possible explanation for why additional therapy made little difference in survival for stage I-III patients is that, given that the tumors did not spread as widely, the surgical procedures were likely to be more effective at removing most of the disease, according to Dr. Tella.
“One of the possibilities is that surgeons were able to get the whole mass out,” Dr. Tella hypothesized in response to a question from attendees. “On the other hand, patients with stage IV ACC may be more likely to have more presence of metastases and so would benefit more greatly from the removal of the primary tumor and then also additional therapy.”
Investigators noted that because of the structure of the registry, they were unable to determine the initiation and duration of chemotherapy, as well as doses of radiation therapy received by the patient.
A more robust database and future stage-specific, prospective clinical trials are needed in order to better understand these findings, Dr. Tella said.
The investigators reported no relevant financial disclosures.
SOURCE: Tella SH et al. Endo 2018.
CHICAGO –
These findings, uncovered using the largest cancer registry in the United States, will help give physicians insight into what the best course of action is for treating their patients, according to presenters.
“Surgical resection of the primary tumor improved survival in all stages of disease, whereas adjuvant therapy with chemotherapy or radiation improved overall survival only in stage IVpatients,” said Sri Harsha Tella, MD, endocrinologist at the University of South Carolina, Columbia. “These results may help the prognostication of patients in treatment decision making.”
Investigators conducted a retrospective study of 3,185 pathologically confirmed cases of ACC, registered into the National Cancer Database between 2004 and 2015.
Patients were mostly women with an average age of 55 years old and private insurance, with a nearly even split of patients with stage I-III (26%) and stage IV ACC (24%). Nearly three-quarters of those studied chose to have surgery, of which 31% chose open resection.
Patients with stage I-III ACC had a significant median survival rate of 63 months, compared with those who did not have surgery who had an average survival of 8 months.
In patients with stage IV ACC, surgery lengthened overall survival to 19 months, compared with 6 months for those without surgery, according to Dr. Tella and fellow investigators.
While surgery did have a greater positive effect on patients’ live spans across all stages, the impact of chemotherapy and radiation was significant only among stage IV patients who had complete surgery.
Those in the stage IV group who were given post-surgery adjuvant chemotherapy were likely to live an average of nearly 9 more months than did those who did not have chemotherapy after radiation (22 vs. 13), while those given radiation therapy saw an increase in survival by 19 months (29 vs. 10). These increases did not affect stage I-III patients, who had a similar rate of survival regardless of additional therapies after their surgery (24 vs. 25 months).
One possible explanation for why additional therapy made little difference in survival for stage I-III patients is that, given that the tumors did not spread as widely, the surgical procedures were likely to be more effective at removing most of the disease, according to Dr. Tella.
“One of the possibilities is that surgeons were able to get the whole mass out,” Dr. Tella hypothesized in response to a question from attendees. “On the other hand, patients with stage IV ACC may be more likely to have more presence of metastases and so would benefit more greatly from the removal of the primary tumor and then also additional therapy.”
Investigators noted that because of the structure of the registry, they were unable to determine the initiation and duration of chemotherapy, as well as doses of radiation therapy received by the patient.
A more robust database and future stage-specific, prospective clinical trials are needed in order to better understand these findings, Dr. Tella said.
The investigators reported no relevant financial disclosures.
SOURCE: Tella SH et al. Endo 2018.
CHICAGO –
These findings, uncovered using the largest cancer registry in the United States, will help give physicians insight into what the best course of action is for treating their patients, according to presenters.
“Surgical resection of the primary tumor improved survival in all stages of disease, whereas adjuvant therapy with chemotherapy or radiation improved overall survival only in stage IVpatients,” said Sri Harsha Tella, MD, endocrinologist at the University of South Carolina, Columbia. “These results may help the prognostication of patients in treatment decision making.”
Investigators conducted a retrospective study of 3,185 pathologically confirmed cases of ACC, registered into the National Cancer Database between 2004 and 2015.
Patients were mostly women with an average age of 55 years old and private insurance, with a nearly even split of patients with stage I-III (26%) and stage IV ACC (24%). Nearly three-quarters of those studied chose to have surgery, of which 31% chose open resection.
Patients with stage I-III ACC had a significant median survival rate of 63 months, compared with those who did not have surgery who had an average survival of 8 months.
In patients with stage IV ACC, surgery lengthened overall survival to 19 months, compared with 6 months for those without surgery, according to Dr. Tella and fellow investigators.
While surgery did have a greater positive effect on patients’ live spans across all stages, the impact of chemotherapy and radiation was significant only among stage IV patients who had complete surgery.
Those in the stage IV group who were given post-surgery adjuvant chemotherapy were likely to live an average of nearly 9 more months than did those who did not have chemotherapy after radiation (22 vs. 13), while those given radiation therapy saw an increase in survival by 19 months (29 vs. 10). These increases did not affect stage I-III patients, who had a similar rate of survival regardless of additional therapies after their surgery (24 vs. 25 months).
One possible explanation for why additional therapy made little difference in survival for stage I-III patients is that, given that the tumors did not spread as widely, the surgical procedures were likely to be more effective at removing most of the disease, according to Dr. Tella.
“One of the possibilities is that surgeons were able to get the whole mass out,” Dr. Tella hypothesized in response to a question from attendees. “On the other hand, patients with stage IV ACC may be more likely to have more presence of metastases and so would benefit more greatly from the removal of the primary tumor and then also additional therapy.”
Investigators noted that because of the structure of the registry, they were unable to determine the initiation and duration of chemotherapy, as well as doses of radiation therapy received by the patient.
A more robust database and future stage-specific, prospective clinical trials are needed in order to better understand these findings, Dr. Tella said.
The investigators reported no relevant financial disclosures.
SOURCE: Tella SH et al. Endo 2018.
REPORTING FROM ENDO 2018
Key clinical point: Patients who undergo surgical resection at all stages are more likely to survive.
Major finding: Patients stage I-III who underwent surgery survived over nearly 8 times longer than non-surgery patients (63 vs. 8 months [P less than .001]).
Study details: Retrospective study of 3,185 adrenal cortical carcinoma cases entered into the National Cancer Database between 2004 and 2015.
Disclosures: The presenter reported no relevant financial disclosures.
Source: Tella SH et al. Endo 2018.
Without reliability, testosterone testing may fall short
CHICAGO – is one addition to the evaluation of men with suspected hypogonadism that is included in the revised clinical practice guideline on testosterone therapy in men with hypogonadism, issued March 17 by the Endocrine Society. The previous guideline was issued in 2010.
“Since 2010, the CDC has provided an accuracy-based standardization program for T (CDC Hormone Standardization Program for Testosterone). Although several commercial laboratories, some assay manufacturers, and some academic laboratories are now CDC certified, most T immunoassay kit manufacturers and local hospital-based laboratories have not been certified. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for TT generally offer higher concentrations of specificity, sensitivity, and precision (especially in the low range) than do most immunoassays. Clinicians should ideally measure TT using a CDC-certified assay or an assay verified by an accuracy-based external quality control program,” according to the guideline.
Diagnosis, treatment, and follow-up of men with suspected hypogonadism often involve nuanced decisions, according to guideline panel chair Shalender Bhasin, MB, an endocrinologist who is professor of medicine at both Harvard Medical School and Brigham and Women’s Hospital, in Boston. The guideline will be published in its entirety in the May 2018 print issue of The Journal of Clinical Endocrinology & Metabolism.
Evaluation for suspected hypogonadism is indicated in men with symptoms and signs of testosterone deficiency – decreased libido, unexplained anemia, and/or osteopenia – and unequivocally and consistently low serum total testosterone and/or free testosterone concentrations, according to the guideline, which is co-sponsored by European Society of Endocrinology and endorsed by the European Academy of Andrology.
The guideline illuminates one area of diagnostic uncertainty that has dogged clinicians: Should one use age-specific testosterone levels? All the guideline authors speaking at the panel, in addition to Dr. Bhasin – Glenn R. Cunningham, MD, Baylor College of Medicine in Houston; Alvin M. Matsumoto, MD, VA Puget Sound Health Care System, Seattle; and Maria A. Yialamas, MD, Brigham and Women’s Hospital, Boston – agreed that age-specific testosterone levels do not improve diagnosis.
“The harmonized Reference range for TT in healthy, nonobese young men (aged 19 to 39 years) was 264 to 916 ng/dL (9.2 to 31.8 nmol/L) using the 2.5th and 97.5th percentile, and 303 to 852 ng/dL (10.5 to 29.5 nmol/L) using the 5th and 95th percentile (31). Clinicians can use this range for all CDC-certified TT assays,” according to the guideline.
Asking about history to explain low testosterone levels is an often overlooked part of patient evaluation. Two known causes of low testosterone in men often are not part of history taking but should be. One is use of opioids. The other is withdrawal from anabolic steroids. The best way to root these out in a history is to ask about any recent surgery and use of anabolic steroids, said Dr. Bhasin, speaking at the annual meeting of the Endocrine Society.
When it works, testosterone can make some men feel better: Testosterone replacement was associated with increased libido, erectile function, and sexual activity. However, testosterone replacement had no effect on energy and/or mood.
Not every man over the age of 65 with low testosterone is a candidate for testosterone replacement. There are some risks associated with its use; PSA may rise within 6 months of starting testosterone replacement, leaving physicians and men facing the issue of whether to have a prostate biopsy. The guideline recommends evaluating the patients with PSA the first time within 3-12 months after the start of therapy. When the test shows that PSA has risen, the decision of whether to have a prostate biopsy is one that should be shared by the patient and physician.
Dr. Bhasin declared financing from the National Institute on Aging, the National Institute of Nursing Research, the Patient-Centered Outcomes Research Institute, AbbVie, Metro International Biotechnology, Alivegen, Abbott, Transition Therapeutics, and Function Promoting Therapies.
SOURCE: ENDO 2018
CHICAGO – is one addition to the evaluation of men with suspected hypogonadism that is included in the revised clinical practice guideline on testosterone therapy in men with hypogonadism, issued March 17 by the Endocrine Society. The previous guideline was issued in 2010.
“Since 2010, the CDC has provided an accuracy-based standardization program for T (CDC Hormone Standardization Program for Testosterone). Although several commercial laboratories, some assay manufacturers, and some academic laboratories are now CDC certified, most T immunoassay kit manufacturers and local hospital-based laboratories have not been certified. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for TT generally offer higher concentrations of specificity, sensitivity, and precision (especially in the low range) than do most immunoassays. Clinicians should ideally measure TT using a CDC-certified assay or an assay verified by an accuracy-based external quality control program,” according to the guideline.
Diagnosis, treatment, and follow-up of men with suspected hypogonadism often involve nuanced decisions, according to guideline panel chair Shalender Bhasin, MB, an endocrinologist who is professor of medicine at both Harvard Medical School and Brigham and Women’s Hospital, in Boston. The guideline will be published in its entirety in the May 2018 print issue of The Journal of Clinical Endocrinology & Metabolism.
Evaluation for suspected hypogonadism is indicated in men with symptoms and signs of testosterone deficiency – decreased libido, unexplained anemia, and/or osteopenia – and unequivocally and consistently low serum total testosterone and/or free testosterone concentrations, according to the guideline, which is co-sponsored by European Society of Endocrinology and endorsed by the European Academy of Andrology.
The guideline illuminates one area of diagnostic uncertainty that has dogged clinicians: Should one use age-specific testosterone levels? All the guideline authors speaking at the panel, in addition to Dr. Bhasin – Glenn R. Cunningham, MD, Baylor College of Medicine in Houston; Alvin M. Matsumoto, MD, VA Puget Sound Health Care System, Seattle; and Maria A. Yialamas, MD, Brigham and Women’s Hospital, Boston – agreed that age-specific testosterone levels do not improve diagnosis.
“The harmonized Reference range for TT in healthy, nonobese young men (aged 19 to 39 years) was 264 to 916 ng/dL (9.2 to 31.8 nmol/L) using the 2.5th and 97.5th percentile, and 303 to 852 ng/dL (10.5 to 29.5 nmol/L) using the 5th and 95th percentile (31). Clinicians can use this range for all CDC-certified TT assays,” according to the guideline.
Asking about history to explain low testosterone levels is an often overlooked part of patient evaluation. Two known causes of low testosterone in men often are not part of history taking but should be. One is use of opioids. The other is withdrawal from anabolic steroids. The best way to root these out in a history is to ask about any recent surgery and use of anabolic steroids, said Dr. Bhasin, speaking at the annual meeting of the Endocrine Society.
When it works, testosterone can make some men feel better: Testosterone replacement was associated with increased libido, erectile function, and sexual activity. However, testosterone replacement had no effect on energy and/or mood.
Not every man over the age of 65 with low testosterone is a candidate for testosterone replacement. There are some risks associated with its use; PSA may rise within 6 months of starting testosterone replacement, leaving physicians and men facing the issue of whether to have a prostate biopsy. The guideline recommends evaluating the patients with PSA the first time within 3-12 months after the start of therapy. When the test shows that PSA has risen, the decision of whether to have a prostate biopsy is one that should be shared by the patient and physician.
Dr. Bhasin declared financing from the National Institute on Aging, the National Institute of Nursing Research, the Patient-Centered Outcomes Research Institute, AbbVie, Metro International Biotechnology, Alivegen, Abbott, Transition Therapeutics, and Function Promoting Therapies.
SOURCE: ENDO 2018
CHICAGO – is one addition to the evaluation of men with suspected hypogonadism that is included in the revised clinical practice guideline on testosterone therapy in men with hypogonadism, issued March 17 by the Endocrine Society. The previous guideline was issued in 2010.
“Since 2010, the CDC has provided an accuracy-based standardization program for T (CDC Hormone Standardization Program for Testosterone). Although several commercial laboratories, some assay manufacturers, and some academic laboratories are now CDC certified, most T immunoassay kit manufacturers and local hospital-based laboratories have not been certified. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for TT generally offer higher concentrations of specificity, sensitivity, and precision (especially in the low range) than do most immunoassays. Clinicians should ideally measure TT using a CDC-certified assay or an assay verified by an accuracy-based external quality control program,” according to the guideline.
Diagnosis, treatment, and follow-up of men with suspected hypogonadism often involve nuanced decisions, according to guideline panel chair Shalender Bhasin, MB, an endocrinologist who is professor of medicine at both Harvard Medical School and Brigham and Women’s Hospital, in Boston. The guideline will be published in its entirety in the May 2018 print issue of The Journal of Clinical Endocrinology & Metabolism.
Evaluation for suspected hypogonadism is indicated in men with symptoms and signs of testosterone deficiency – decreased libido, unexplained anemia, and/or osteopenia – and unequivocally and consistently low serum total testosterone and/or free testosterone concentrations, according to the guideline, which is co-sponsored by European Society of Endocrinology and endorsed by the European Academy of Andrology.
The guideline illuminates one area of diagnostic uncertainty that has dogged clinicians: Should one use age-specific testosterone levels? All the guideline authors speaking at the panel, in addition to Dr. Bhasin – Glenn R. Cunningham, MD, Baylor College of Medicine in Houston; Alvin M. Matsumoto, MD, VA Puget Sound Health Care System, Seattle; and Maria A. Yialamas, MD, Brigham and Women’s Hospital, Boston – agreed that age-specific testosterone levels do not improve diagnosis.
“The harmonized Reference range for TT in healthy, nonobese young men (aged 19 to 39 years) was 264 to 916 ng/dL (9.2 to 31.8 nmol/L) using the 2.5th and 97.5th percentile, and 303 to 852 ng/dL (10.5 to 29.5 nmol/L) using the 5th and 95th percentile (31). Clinicians can use this range for all CDC-certified TT assays,” according to the guideline.
Asking about history to explain low testosterone levels is an often overlooked part of patient evaluation. Two known causes of low testosterone in men often are not part of history taking but should be. One is use of opioids. The other is withdrawal from anabolic steroids. The best way to root these out in a history is to ask about any recent surgery and use of anabolic steroids, said Dr. Bhasin, speaking at the annual meeting of the Endocrine Society.
When it works, testosterone can make some men feel better: Testosterone replacement was associated with increased libido, erectile function, and sexual activity. However, testosterone replacement had no effect on energy and/or mood.
Not every man over the age of 65 with low testosterone is a candidate for testosterone replacement. There are some risks associated with its use; PSA may rise within 6 months of starting testosterone replacement, leaving physicians and men facing the issue of whether to have a prostate biopsy. The guideline recommends evaluating the patients with PSA the first time within 3-12 months after the start of therapy. When the test shows that PSA has risen, the decision of whether to have a prostate biopsy is one that should be shared by the patient and physician.
Dr. Bhasin declared financing from the National Institute on Aging, the National Institute of Nursing Research, the Patient-Centered Outcomes Research Institute, AbbVie, Metro International Biotechnology, Alivegen, Abbott, Transition Therapeutics, and Function Promoting Therapies.
SOURCE: ENDO 2018
REPORTING FROM ENDO 2018
Axitinib/avelumab combo shows preliminary efficacy in RCC
The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
FROM THE LANCET ONCOLOGY
Key clinical point: The targeted-immune combination of axitinib and avelumab had manageable toxicity and encouraging preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC).
Major finding: Out of 55 patients enrolled, 26 (53%) had a response, including 3 (6%) who had complete responses.
Study details: A dose-expansion and dose-finding phase 1b study including 55 patients with advanced clear-cell RCC.
Disclosures: Funding for the study came from Pfizer and Merck. Study authors declared interests related to several companies, including Pfizer, Merck, Bristol-Myers Squibb, Novartis, Roche/Genentech.
Source: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
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The antitumor activity of axitinib and avelumab in this study indicate the potential clinical benefit of targeted-immune combinations for advanced renal cell carcinoma (RCC), according to Viktor Grünwald, MD, PhD.
“Further studies are warranted to explore whether a first-line targeted-immune combination might overcome the standard of sequential targeted and immune therapies,” Dr. Grünwald said in an editorial.
The current absence of long-term safety data for the combination approach is limiting in terms of making definitive conclusions about the toxicity of axitinib and avelumab as a first line combination therapy for advanced clear-cell RCC, Dr. Grünwald wrote.
Even so, axitinib has a “low” incidence of hepatic toxicity, making it a “preferable” agent to evaluate in targeted-immune combination trials such as JAVELIN Renal 100, he added.
Objective responses in JAVELIN Renal 100 were seen in 32 out of 55 patients (58%), of which 3 patients (6%) were complete responses, according to reported data.
Similar findings previously reported for the immune-immune combination of ipilimumab and nivolumab versus sunitinib. In that study, patients receiving the immune-immune combination had an overall response rate of 42% and complete response rate of 9%, while the group patients receiving sunitinib had overall and complete response rates of 27% and 1%, respectively, he said.
“With the dawn of immune-immune and targeted-immune combinations, for the first time in a decade, major progress towards improving the median overall survival and possibly delivering cure to some of our patients with metastatic renal-cell carcinoma seems to have been made,” Dr. Grünwald said.
Viktor Grünwald, MD, PhD, is with the department of hematology, haemostasis, oncology, and stem cell transplantation at Hannover Medical School, Germany. These comments are based on an editorial accompanying the report (Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045[18]30126-8). Dr. Grünwald disclosed ties to Bristol-Myers Squibb, Merck Sharp and Dohme, Ipsen, Novartis, Roche, AstraZeneca, Pfizer, Cerulean, Eisai, and EUSA Pharma.
Court: State cannot sue over religious exemption expansion
Massachusetts cannot sue the Trump administration for broadening exemptions to the Affordable Care Act’s contraceptive mandate, a district court has ruled.
In a March decision, the U.S. District Court for the District of Massachusetts concluded that the state lacks standing to sue the federal government and that it could not prove that its residents would be harmed by the expanded exemption.
Under two regulations, issued in October 2017 in the Federal Register, the Trump administration allowed that an expanded group of employers and insurers can object to paying for contraception coverage on religious or moral grounds. The new policy “better balances the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions,” according to the rule issued by the departments of Health & Human Services, Labor, and Treasury.
Several state attorneys general sued over the rules, including Massachusetts Attorney General Maura Healey (D). Ms. Healey argued that the rules violates women’s equal protection rights by restricting their ability to access contraception. The lawsuit also claimed the narrowing of the mandate allowed employers to unconstitutionally impose their religious and moral beliefs on employees.
“The [rules] jeopardize the health care of women in Massachusetts and nationwide, promote the religious freedom of corporations over the autonomy and health of women, and leave the states to bear additional health care costs both with regard to contraceptive and prenatal care as well as other services associated with unintended pregnancies and related negative health outcomes for both women and their children,” the lawsuit stated.
In his March 12 opinion however, U.S. District Judge Nathaniel M. Gorton dismissed the state’s claims, ruling that Massachusetts failed to prove its citizens will suffer future injury from the exemption expansion. The judge noted a 2017 law passed by Massachusetts called the ACCESS Act that requires certain employer-sponsored health plans to cover contraceptives without imposing out-of-pocket costs on employees. This law and other state regulations make Massachusetts less likely than women in other states to be affected negatively by the expanded exemption, said Judge Gorton, who was appointed to the bench by President George H.W. Bush.
In a statement, Ms. Healey said the state was disappointed in the decision, but remained steadfast in its commitment to “ensuring affordable and reliable reproductive health care for women.”
“Access to contraceptive coverage is a critical issue for the health, equality, and economic well-being of women and their families, and we will continue to fight for these protections.” Ms. Healey said.
The legal fight over the ACA’s contraceptive mandate exemption is far from over. The Massachusetts decision comes after federal judges in California and Pennsylvania halted the administration’s exemption rules. In December 2017, U.S. District Judge Haywood Gilliam Jr. temporarily blocked the exemption extension from going forward in favor of California and four other states that joined the lawsuit – New York, Delaware, Maryland, and Virginia. Earlier that month, U.S. District Judge Wendy Beetlestone ruled similarly in a decision for the U.S. District Court for the Eastern District of Pennsylvania. Both Mr. Gilliam and Ms. Beetlestone were appointed to the bench by President Obama.
The Trump administration has indicated that it plans to appeal the rulings. In a summary of the rules, the administration said the new policies will “better balance the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions.”
Massachusetts cannot sue the Trump administration for broadening exemptions to the Affordable Care Act’s contraceptive mandate, a district court has ruled.
In a March decision, the U.S. District Court for the District of Massachusetts concluded that the state lacks standing to sue the federal government and that it could not prove that its residents would be harmed by the expanded exemption.
Under two regulations, issued in October 2017 in the Federal Register, the Trump administration allowed that an expanded group of employers and insurers can object to paying for contraception coverage on religious or moral grounds. The new policy “better balances the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions,” according to the rule issued by the departments of Health & Human Services, Labor, and Treasury.
Several state attorneys general sued over the rules, including Massachusetts Attorney General Maura Healey (D). Ms. Healey argued that the rules violates women’s equal protection rights by restricting their ability to access contraception. The lawsuit also claimed the narrowing of the mandate allowed employers to unconstitutionally impose their religious and moral beliefs on employees.
“The [rules] jeopardize the health care of women in Massachusetts and nationwide, promote the religious freedom of corporations over the autonomy and health of women, and leave the states to bear additional health care costs both with regard to contraceptive and prenatal care as well as other services associated with unintended pregnancies and related negative health outcomes for both women and their children,” the lawsuit stated.
In his March 12 opinion however, U.S. District Judge Nathaniel M. Gorton dismissed the state’s claims, ruling that Massachusetts failed to prove its citizens will suffer future injury from the exemption expansion. The judge noted a 2017 law passed by Massachusetts called the ACCESS Act that requires certain employer-sponsored health plans to cover contraceptives without imposing out-of-pocket costs on employees. This law and other state regulations make Massachusetts less likely than women in other states to be affected negatively by the expanded exemption, said Judge Gorton, who was appointed to the bench by President George H.W. Bush.
In a statement, Ms. Healey said the state was disappointed in the decision, but remained steadfast in its commitment to “ensuring affordable and reliable reproductive health care for women.”
“Access to contraceptive coverage is a critical issue for the health, equality, and economic well-being of women and their families, and we will continue to fight for these protections.” Ms. Healey said.
The legal fight over the ACA’s contraceptive mandate exemption is far from over. The Massachusetts decision comes after federal judges in California and Pennsylvania halted the administration’s exemption rules. In December 2017, U.S. District Judge Haywood Gilliam Jr. temporarily blocked the exemption extension from going forward in favor of California and four other states that joined the lawsuit – New York, Delaware, Maryland, and Virginia. Earlier that month, U.S. District Judge Wendy Beetlestone ruled similarly in a decision for the U.S. District Court for the Eastern District of Pennsylvania. Both Mr. Gilliam and Ms. Beetlestone were appointed to the bench by President Obama.
The Trump administration has indicated that it plans to appeal the rulings. In a summary of the rules, the administration said the new policies will “better balance the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions.”
Massachusetts cannot sue the Trump administration for broadening exemptions to the Affordable Care Act’s contraceptive mandate, a district court has ruled.
In a March decision, the U.S. District Court for the District of Massachusetts concluded that the state lacks standing to sue the federal government and that it could not prove that its residents would be harmed by the expanded exemption.
Under two regulations, issued in October 2017 in the Federal Register, the Trump administration allowed that an expanded group of employers and insurers can object to paying for contraception coverage on religious or moral grounds. The new policy “better balances the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions,” according to the rule issued by the departments of Health & Human Services, Labor, and Treasury.
Several state attorneys general sued over the rules, including Massachusetts Attorney General Maura Healey (D). Ms. Healey argued that the rules violates women’s equal protection rights by restricting their ability to access contraception. The lawsuit also claimed the narrowing of the mandate allowed employers to unconstitutionally impose their religious and moral beliefs on employees.
“The [rules] jeopardize the health care of women in Massachusetts and nationwide, promote the religious freedom of corporations over the autonomy and health of women, and leave the states to bear additional health care costs both with regard to contraceptive and prenatal care as well as other services associated with unintended pregnancies and related negative health outcomes for both women and their children,” the lawsuit stated.
In his March 12 opinion however, U.S. District Judge Nathaniel M. Gorton dismissed the state’s claims, ruling that Massachusetts failed to prove its citizens will suffer future injury from the exemption expansion. The judge noted a 2017 law passed by Massachusetts called the ACCESS Act that requires certain employer-sponsored health plans to cover contraceptives without imposing out-of-pocket costs on employees. This law and other state regulations make Massachusetts less likely than women in other states to be affected negatively by the expanded exemption, said Judge Gorton, who was appointed to the bench by President George H.W. Bush.
In a statement, Ms. Healey said the state was disappointed in the decision, but remained steadfast in its commitment to “ensuring affordable and reliable reproductive health care for women.”
“Access to contraceptive coverage is a critical issue for the health, equality, and economic well-being of women and their families, and we will continue to fight for these protections.” Ms. Healey said.
The legal fight over the ACA’s contraceptive mandate exemption is far from over. The Massachusetts decision comes after federal judges in California and Pennsylvania halted the administration’s exemption rules. In December 2017, U.S. District Judge Haywood Gilliam Jr. temporarily blocked the exemption extension from going forward in favor of California and four other states that joined the lawsuit – New York, Delaware, Maryland, and Virginia. Earlier that month, U.S. District Judge Wendy Beetlestone ruled similarly in a decision for the U.S. District Court for the Eastern District of Pennsylvania. Both Mr. Gilliam and Ms. Beetlestone were appointed to the bench by President Obama.
The Trump administration has indicated that it plans to appeal the rulings. In a summary of the rules, the administration said the new policies will “better balance the government’s interest in promoting coverage for contraceptive and sterilization services with the government’s interests in providing conscience protections for entities with sincerely held moral convictions.”
DOACs may be beneficial in post-op atrial fib after CABG
SAN DIEGO – The use of direct oral anticoagulants were not significantly different from warfarin for safety and efficacy in cases of postoperative atrial fibrillation following coronary artery bypass grafting, according to results from a single-center study.
In fact, , which suggests a potential for reduced hospital stay-related costs. “There are several different niche populations for which the DOACs have not been studied,” one of the study authors, Ammie J. Patel, PharmD, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This provides the opportunity for institutions and hospitals to study the use of these drugs in non-traditional ways.”
Dr. Patel, of Temple University, Philadelphia, said that postoperative atrial fibrillation occurs in about 30% of patients following CABG and that new-onset postoperative atrial fibrillation after CABG has been linked to a 21% increase in relative mortality.
Noting that patients with planned major surgery were excluded from RE-LY, ROCKET AF, ARISTOTLE, and other pivotal clinical trials of DOACs, she and her research mentor, Rachael Durie, PharmD, retrospectively evaluated the safety and efficacy of DOACs in 285 cases of new-onset postoperative atrial fibrillation following CABG performed at Jersey Shore University Medical Center, Neptune, N.J., between July 1, 2014, and June 30, 2016. They hypothesized that using DOACs in this patient population might offer advantages over warfarin, including rapid onset and earlier hospital discharge, fewer drug interactions, and no coagulation monitoring.
Of the 146 patients on anticoagulants, 79 were discharged on warfarin, 43 on apixaban, 20 on rivaroxaban, and 4 on dabigatran. The other 139 patients were not anticoagulated for various reasons, one of which included normal sinus rhythm at discharge.
The researchers found that the DOACs were not significantly different from warfarin for efficacy endpoints in stroke (P = 0.23) or systemic embolism (P = 0.68). Safety endpoints also were similar among all groups for major bleeding (P = 0.57) or minor bleeding (P = 0.63). Median post-CABG length of stay was significantly longer in the warfarin group (8 days, P = 0.005), compared with dabigatran (7.5 days), rivaroxaban (6.5 days), and apixaban (6 days). In addition, the median total hospital length of stay was significantly longer with warfarin (11 days, P = 0.004), compared with rivaroxaban (8.5 days) and apixaban (9 days), but not compared with dabigatran (12 days).
Dr. Patel acknowledged that the study’s retrospective design and small sample size are limitations and said that larger prospective trials are warranted to confirm these results. She reported having no financial disclosures.
SOURCE: Patel AJ et al. THSNA 2018. Poster 64.
SAN DIEGO – The use of direct oral anticoagulants were not significantly different from warfarin for safety and efficacy in cases of postoperative atrial fibrillation following coronary artery bypass grafting, according to results from a single-center study.
In fact, , which suggests a potential for reduced hospital stay-related costs. “There are several different niche populations for which the DOACs have not been studied,” one of the study authors, Ammie J. Patel, PharmD, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This provides the opportunity for institutions and hospitals to study the use of these drugs in non-traditional ways.”
Dr. Patel, of Temple University, Philadelphia, said that postoperative atrial fibrillation occurs in about 30% of patients following CABG and that new-onset postoperative atrial fibrillation after CABG has been linked to a 21% increase in relative mortality.
Noting that patients with planned major surgery were excluded from RE-LY, ROCKET AF, ARISTOTLE, and other pivotal clinical trials of DOACs, she and her research mentor, Rachael Durie, PharmD, retrospectively evaluated the safety and efficacy of DOACs in 285 cases of new-onset postoperative atrial fibrillation following CABG performed at Jersey Shore University Medical Center, Neptune, N.J., between July 1, 2014, and June 30, 2016. They hypothesized that using DOACs in this patient population might offer advantages over warfarin, including rapid onset and earlier hospital discharge, fewer drug interactions, and no coagulation monitoring.
Of the 146 patients on anticoagulants, 79 were discharged on warfarin, 43 on apixaban, 20 on rivaroxaban, and 4 on dabigatran. The other 139 patients were not anticoagulated for various reasons, one of which included normal sinus rhythm at discharge.
The researchers found that the DOACs were not significantly different from warfarin for efficacy endpoints in stroke (P = 0.23) or systemic embolism (P = 0.68). Safety endpoints also were similar among all groups for major bleeding (P = 0.57) or minor bleeding (P = 0.63). Median post-CABG length of stay was significantly longer in the warfarin group (8 days, P = 0.005), compared with dabigatran (7.5 days), rivaroxaban (6.5 days), and apixaban (6 days). In addition, the median total hospital length of stay was significantly longer with warfarin (11 days, P = 0.004), compared with rivaroxaban (8.5 days) and apixaban (9 days), but not compared with dabigatran (12 days).
Dr. Patel acknowledged that the study’s retrospective design and small sample size are limitations and said that larger prospective trials are warranted to confirm these results. She reported having no financial disclosures.
SOURCE: Patel AJ et al. THSNA 2018. Poster 64.
SAN DIEGO – The use of direct oral anticoagulants were not significantly different from warfarin for safety and efficacy in cases of postoperative atrial fibrillation following coronary artery bypass grafting, according to results from a single-center study.
In fact, , which suggests a potential for reduced hospital stay-related costs. “There are several different niche populations for which the DOACs have not been studied,” one of the study authors, Ammie J. Patel, PharmD, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This provides the opportunity for institutions and hospitals to study the use of these drugs in non-traditional ways.”
Dr. Patel, of Temple University, Philadelphia, said that postoperative atrial fibrillation occurs in about 30% of patients following CABG and that new-onset postoperative atrial fibrillation after CABG has been linked to a 21% increase in relative mortality.
Noting that patients with planned major surgery were excluded from RE-LY, ROCKET AF, ARISTOTLE, and other pivotal clinical trials of DOACs, she and her research mentor, Rachael Durie, PharmD, retrospectively evaluated the safety and efficacy of DOACs in 285 cases of new-onset postoperative atrial fibrillation following CABG performed at Jersey Shore University Medical Center, Neptune, N.J., between July 1, 2014, and June 30, 2016. They hypothesized that using DOACs in this patient population might offer advantages over warfarin, including rapid onset and earlier hospital discharge, fewer drug interactions, and no coagulation monitoring.
Of the 146 patients on anticoagulants, 79 were discharged on warfarin, 43 on apixaban, 20 on rivaroxaban, and 4 on dabigatran. The other 139 patients were not anticoagulated for various reasons, one of which included normal sinus rhythm at discharge.
The researchers found that the DOACs were not significantly different from warfarin for efficacy endpoints in stroke (P = 0.23) or systemic embolism (P = 0.68). Safety endpoints also were similar among all groups for major bleeding (P = 0.57) or minor bleeding (P = 0.63). Median post-CABG length of stay was significantly longer in the warfarin group (8 days, P = 0.005), compared with dabigatran (7.5 days), rivaroxaban (6.5 days), and apixaban (6 days). In addition, the median total hospital length of stay was significantly longer with warfarin (11 days, P = 0.004), compared with rivaroxaban (8.5 days) and apixaban (9 days), but not compared with dabigatran (12 days).
Dr. Patel acknowledged that the study’s retrospective design and small sample size are limitations and said that larger prospective trials are warranted to confirm these results. She reported having no financial disclosures.
SOURCE: Patel AJ et al. THSNA 2018. Poster 64.
REPORTING FROM THSNA 2018
Key clinical point: DOACs may be safe and effective alternatives to warfarin in postoperative atrial fibrillation after CABG.
Major finding: DOACs were not significantly different from warfarin for efficacy endpoints in stroke (P = 0.23) or systemic embolism (P = 0.68).
Study details: A retrospective, single-center study of DOACs in 285 cases of new-onset postoperative atrial fibrillation following CABG.
Disclosures: Dr. Patel reported having no financial disclosures.
Source: Patel AJ et al. THSNA 2018. Poster 64.
More evidence links increased BMI to higher multiple myeloma risk
A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.
“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”
Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.
Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.
Dr. Marinac and her team identified a total of 205 men from the HPFS cohort and 370 women (325 NHS, 45 WHS) with confirmed diagnoses of MM. The BMIs of those participants ranged from 23.8-25.8 kg/m2 at baseline and from 21.3-23.0 kg/m2 in young adulthood. Across all cohorts, each 5 kg/m2 increase in cumulative average adult BMI significantly increased the risk of MM by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.29).
In addition, the MM risk rose almost 30% for every 5 kg/m2 increase in young adult BMI (HR, 1.28; 95% CI, 1.12-1.47). Increased risk was not strictly related to changes in BMI but to incremental weight gain since young adulthood. (pooled HR, 1.04; 95% CI, 1.00-1.08; P = 0.03).
The study confirmed correlations between weight gain and increased MM risk, however, it also had certain limitations. For example, much of the data concerning weight, height, and physical activity were all self-reported. Another limitation is the sociodemographic heterogeneity of the study population.
Despite those limitations, Dr. Marinac emphasized that the study results add to evidence concerning weight gain and MM risk.
“Our findings support the growing body of literature demonstrating that a high BMI both early and later in adulthood is associated with the risk of MM, and suggest that maintaining a healthy body weight throughout life may be an important component to a much-needed MM prevention strategy,” wrote Dr. Marinac, who also is affiliated with the Harvard T.H. Chan School of Public Health, also in Boston.
“Further larger-scale studies aimed at clarifying the influence of obesity timing and duration and at directly evaluating the role of weight loss, ideally conducted in diverse prospective study populations and in [monoclonal gammopathy of undetermined significance] patients, will be important for elaborating the role of weight maintenance in MM prevention and for identifying high risk subgroups of patients that may benefit from weight loss.”
None of the researchers had competing financial interests to disclose.
SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.
“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”
Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.
Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.
Dr. Marinac and her team identified a total of 205 men from the HPFS cohort and 370 women (325 NHS, 45 WHS) with confirmed diagnoses of MM. The BMIs of those participants ranged from 23.8-25.8 kg/m2 at baseline and from 21.3-23.0 kg/m2 in young adulthood. Across all cohorts, each 5 kg/m2 increase in cumulative average adult BMI significantly increased the risk of MM by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.29).
In addition, the MM risk rose almost 30% for every 5 kg/m2 increase in young adult BMI (HR, 1.28; 95% CI, 1.12-1.47). Increased risk was not strictly related to changes in BMI but to incremental weight gain since young adulthood. (pooled HR, 1.04; 95% CI, 1.00-1.08; P = 0.03).
The study confirmed correlations between weight gain and increased MM risk, however, it also had certain limitations. For example, much of the data concerning weight, height, and physical activity were all self-reported. Another limitation is the sociodemographic heterogeneity of the study population.
Despite those limitations, Dr. Marinac emphasized that the study results add to evidence concerning weight gain and MM risk.
“Our findings support the growing body of literature demonstrating that a high BMI both early and later in adulthood is associated with the risk of MM, and suggest that maintaining a healthy body weight throughout life may be an important component to a much-needed MM prevention strategy,” wrote Dr. Marinac, who also is affiliated with the Harvard T.H. Chan School of Public Health, also in Boston.
“Further larger-scale studies aimed at clarifying the influence of obesity timing and duration and at directly evaluating the role of weight loss, ideally conducted in diverse prospective study populations and in [monoclonal gammopathy of undetermined significance] patients, will be important for elaborating the role of weight maintenance in MM prevention and for identifying high risk subgroups of patients that may benefit from weight loss.”
None of the researchers had competing financial interests to disclose.
SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.
“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”
Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.
Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.
Dr. Marinac and her team identified a total of 205 men from the HPFS cohort and 370 women (325 NHS, 45 WHS) with confirmed diagnoses of MM. The BMIs of those participants ranged from 23.8-25.8 kg/m2 at baseline and from 21.3-23.0 kg/m2 in young adulthood. Across all cohorts, each 5 kg/m2 increase in cumulative average adult BMI significantly increased the risk of MM by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.29).
In addition, the MM risk rose almost 30% for every 5 kg/m2 increase in young adult BMI (HR, 1.28; 95% CI, 1.12-1.47). Increased risk was not strictly related to changes in BMI but to incremental weight gain since young adulthood. (pooled HR, 1.04; 95% CI, 1.00-1.08; P = 0.03).
The study confirmed correlations between weight gain and increased MM risk, however, it also had certain limitations. For example, much of the data concerning weight, height, and physical activity were all self-reported. Another limitation is the sociodemographic heterogeneity of the study population.
Despite those limitations, Dr. Marinac emphasized that the study results add to evidence concerning weight gain and MM risk.
“Our findings support the growing body of literature demonstrating that a high BMI both early and later in adulthood is associated with the risk of MM, and suggest that maintaining a healthy body weight throughout life may be an important component to a much-needed MM prevention strategy,” wrote Dr. Marinac, who also is affiliated with the Harvard T.H. Chan School of Public Health, also in Boston.
“Further larger-scale studies aimed at clarifying the influence of obesity timing and duration and at directly evaluating the role of weight loss, ideally conducted in diverse prospective study populations and in [monoclonal gammopathy of undetermined significance] patients, will be important for elaborating the role of weight maintenance in MM prevention and for identifying high risk subgroups of patients that may benefit from weight loss.”
None of the researchers had competing financial interests to disclose.
SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
FROM BRITISH JOURNAL OF CANCER
Key clinical point: Moderate increases in body mass index (BMI) can dramatically increase the risk of developing multiple myeloma (MM).
Major finding: Each 5 kg/m2 increase in cumulative average adult BMI significantly increased the risk of MM by 17%.
Study details: Prospective analysis of 49,374 men and 153,260 women from three databases.
Disclosures: None of the researchers had competing financial interests to disclose.
Source: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.