A Call to Address Sexual Harassment and Gender Discrimination in Medicine

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PART I
Reports of sexual harassment and gender discrimination have dominated news headlines, and the #MeToo movement has brought the scope and severity of discriminatory behavior to the forefront of public consciousness. The #MeToo movement has raised national and global awareness of gender discrimination and sexual harassment in all industries and has given rise to Time’s Up initiative within health care.
Academic medicine has not been immune to workplace gender discrimination and sexual harassment as has been vastly reported in the literature and clearly documented in the 2018 National Academies of Sciences, Engineering, and Medicine report, which points out that … “the cumulative effect of sexual harassment is a significant and costly loss of talent in academic science, engineering, and medicine, which has consequences for advancing the nation’s economic and social well-being and its overall public health.”1 
With the increasing recognition that healthcare is an environment especially prone to inequality, gender discrimination and sexual discrimination, the Time’s Up national organization, supported by the Time’s Up Legal Defense Fund, launched the Time’s Up initiative for health care workers on March 1, 2019.2,3 The overarching goal of this initiative is to expose workplace inequalities; drive policy and legislative changes focused on equal pay, equal opportunity, and equal work environments; and support safe, fair, and dignified work for women in health care. 2,3
This article, presented over the next three issues of Vascular Specialist, will present data on the ongoing problem of sexual harassment in medicine, discuss why the problem is prevalent in academic medicine, and provide recommendations for mitigating the problem in our workplace.

Defining & Measuring Sexual Harassment
Although commonly referred to as “sex discrimination,” sexual harassment differs from sexual discrimination. Sex discrimination refers to an employees’ denial of civil rights, raises, job opportunities, employment or a demotion or other mistreatments based on sex. On the other hand, sexual harassment relates to behavior that is inappropriate or offensive. A 2018 report from the National Academies Press defined sexual harassment (a form of discrimination) as comprising three categories of behavior: gender harassment – verbal and nonverbal behaviors that convey hostility, objectification, exclusion, or second-class status about members of one sex; unwanted sexual attention – verbal or physical unwelcome sexual advances, which can include assault; and sexual coercion – when favorable professional or educational treatment is conditional based on sexual activity.1
During 1995-2016, more than 7,000 health care service employees filed claims of sexual harassment with the Equal Employment Opportunity Commission. While this number may seem large, the number of official reports severely undervalues the prevalence of sexual discrimination in U.S. health care.1 Prevalence is best determined using representative validated surveys that rely on firsthand experience or observation of the behavior(s) without requiring the respondent to label those behaviors.

Environments at Risk for Sexual Harassment 
Research reveals that academic settings in the fields of science exhibit characteristics that create high levels of risk for sexual harassment to occur. These environments historically are male dominated, tolerate sexually harassing behavior, and create a hierarchy in which men hold most of the positions of power and authority. Moreover, dependent relationships often exist between these gatekeepers and those subordinate to them, with gatekeepers directly influencing the career advancement of those subordinates.1
The greatest predictor of sexual harassment in the workplace is the organizational climate, which refers to the tolerance for sexual harassment and is measured on three elements: a lack of sanctions against offenders; a perceived risk to those who report sexually harassing behavior; and the perception that one’s report of sexually harassing behavior will not be taken seriously.1 Women are less likely to be directly harassed in environments that do not tolerate harassing behaviors or have a strong, clear, transparent consequence for these behaviors.  

Sexual Harassment in Academic Medicine
Academic medicine has the highest rate of gender and sexual harassment in the health care industry, with about 50% of female academic physicians reporting incidents of sexual harassment.1 A recent survey suggests that more than half (58%) of women surgeons experienced sexual harassment within just the previous year alone.4 The conditions that increase the risk of sexual harassment against women – male-dominated hierarchical environments and organizational tolerance of sexual harassment – still prevail in academic medicine. 
Higher-education environments are perceived as permissive environments in part because when targets report sexual harassment, they are retaliated against or there are few consequences for the perpetrator. Academic institutions are replete with cases in which the conduct of offenders is regarded as an open secret, but there are no sanctions for that bad behavior. These offenders often are perceived as superstars in their particular substantive area. Because they hold valued grants or national status within their specialty area, they often receive preferential treatment and are not held accountable for gender-biased and sexually harassing behavior. Interview data regarding sexual harassment in academic medicine reveals that interview respondents and other colleagues often know which individuals have a history of sexually harassing behavior. Both men and women warn colleagues of these perpetrators – knowing that calling out or reporting these behaviors is fruitless – and that the best manner for dealing with their behavior is to avoid or ignore it. This normalization of sexual harassment and gender bias was noted, unfortunately, to fuel similar behavior in new cohorts of medicine faculty.1 
Sexual harassment of women in academic medicine starts in medical school. Female medical students are significantly more likely to experience sexual harassment by faculty and staff than are graduate or undergraduate students. Sexual harassment continues into residency training with residency described as “breeding grounds for abusive behavior by superiors.”1 Interview studies report that both men and women trainees widely accept harassing behavior at this stage of their training. The expectation of abusive and grueling conditions during residency caused several respondents to view sexual harassment as part of a continuum that they were expected to endure. Female residents in surgery and emergency medicine are more likely to be harassed than those in other specialties because of the high value placed on a hierarchical and authoritative workplace. Once out of residency, the sexual harassment of women in the workplace continues. A recent meta-analysis reveals that 58% of women faculty experience sexual harassment at work. Academic medicine has the second-highest rate of sexual harassment, behind the military (69%), as compared with all other workplaces. Women physicians of color experience more harassment (as a combination of sexual and racial harassment) than do white women physicians.1 

Why Women Are Not Likely to Report Sexual Harassment
Only 25% of targets file formal reports with their employer, with even fewer taking claims to court. These numbers are even lower for women in the military and academic medicine, where formal reporting is the last resort for the victims. The reluctance to use formal reporting mechanisms is rooted in the “fear of blame, disbelief, inaction, retaliation, humiliation, ostracism, and the damage to one’s career and reputation.”1 Targets may perceive that there seem to be few benefits and high costs for reporting. Women and nonwhites often resist calling bad behavior “discrimination” because that increases their loss of control and victimhood.1 Women frequently perceive that grievance procedures favor the institution over the individual, and research has proven that women face retaliation, both professional and social, for speaking out. Furthermore, stark power differentials between the target and the perpetrator exacerbate the reluctance to report and the fear of retaliation. The overall effects can be long lasting. 

References:
1. National Academies of Sciences, Engineering, and Medicine. Sexual Harassment of Women: Climate, Culture, and Consequences in Academic Sciences, Engineering, and Medicine. The National Academies Press, Washington, DC; 2018. doi. 10.17226/24994.
2. Choo EK et al. From #MeToo to #TimesUp in Health Care: Can a Culture of Accountability End Inequity and Harassment? Lancet. 2019 Feb 9;393(10171):499-502.
3. Choo EK et al. Time’s Up for Medicine? Only Time Will Tell. N Engl J Med. 2018 Oct 25;379(17):1592-3.
4. Medicine Has Its Own #MeToo Problems. Can Time’s Up Healthcare Fix It? 

Dr. Mitchell is a vascular surgeon at Salem (Ore.) Hospital; Dr. Drudi is as vascular surgery resident at McGill University, Montreal; Dr. Brown is a professor of surgery at the Medical College of Wisconsin. Milwaukee; Dr. Sachdev-Ost is an associate professor of surgery at the University of Pittsburgh Medical Center.

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PART I
Reports of sexual harassment and gender discrimination have dominated news headlines, and the #MeToo movement has brought the scope and severity of discriminatory behavior to the forefront of public consciousness. The #MeToo movement has raised national and global awareness of gender discrimination and sexual harassment in all industries and has given rise to Time’s Up initiative within health care.
Academic medicine has not been immune to workplace gender discrimination and sexual harassment as has been vastly reported in the literature and clearly documented in the 2018 National Academies of Sciences, Engineering, and Medicine report, which points out that … “the cumulative effect of sexual harassment is a significant and costly loss of talent in academic science, engineering, and medicine, which has consequences for advancing the nation’s economic and social well-being and its overall public health.”1 
With the increasing recognition that healthcare is an environment especially prone to inequality, gender discrimination and sexual discrimination, the Time’s Up national organization, supported by the Time’s Up Legal Defense Fund, launched the Time’s Up initiative for health care workers on March 1, 2019.2,3 The overarching goal of this initiative is to expose workplace inequalities; drive policy and legislative changes focused on equal pay, equal opportunity, and equal work environments; and support safe, fair, and dignified work for women in health care. 2,3
This article, presented over the next three issues of Vascular Specialist, will present data on the ongoing problem of sexual harassment in medicine, discuss why the problem is prevalent in academic medicine, and provide recommendations for mitigating the problem in our workplace.

Defining & Measuring Sexual Harassment
Although commonly referred to as “sex discrimination,” sexual harassment differs from sexual discrimination. Sex discrimination refers to an employees’ denial of civil rights, raises, job opportunities, employment or a demotion or other mistreatments based on sex. On the other hand, sexual harassment relates to behavior that is inappropriate or offensive. A 2018 report from the National Academies Press defined sexual harassment (a form of discrimination) as comprising three categories of behavior: gender harassment – verbal and nonverbal behaviors that convey hostility, objectification, exclusion, or second-class status about members of one sex; unwanted sexual attention – verbal or physical unwelcome sexual advances, which can include assault; and sexual coercion – when favorable professional or educational treatment is conditional based on sexual activity.1
During 1995-2016, more than 7,000 health care service employees filed claims of sexual harassment with the Equal Employment Opportunity Commission. While this number may seem large, the number of official reports severely undervalues the prevalence of sexual discrimination in U.S. health care.1 Prevalence is best determined using representative validated surveys that rely on firsthand experience or observation of the behavior(s) without requiring the respondent to label those behaviors.

Environments at Risk for Sexual Harassment 
Research reveals that academic settings in the fields of science exhibit characteristics that create high levels of risk for sexual harassment to occur. These environments historically are male dominated, tolerate sexually harassing behavior, and create a hierarchy in which men hold most of the positions of power and authority. Moreover, dependent relationships often exist between these gatekeepers and those subordinate to them, with gatekeepers directly influencing the career advancement of those subordinates.1
The greatest predictor of sexual harassment in the workplace is the organizational climate, which refers to the tolerance for sexual harassment and is measured on three elements: a lack of sanctions against offenders; a perceived risk to those who report sexually harassing behavior; and the perception that one’s report of sexually harassing behavior will not be taken seriously.1 Women are less likely to be directly harassed in environments that do not tolerate harassing behaviors or have a strong, clear, transparent consequence for these behaviors.  

Sexual Harassment in Academic Medicine
Academic medicine has the highest rate of gender and sexual harassment in the health care industry, with about 50% of female academic physicians reporting incidents of sexual harassment.1 A recent survey suggests that more than half (58%) of women surgeons experienced sexual harassment within just the previous year alone.4 The conditions that increase the risk of sexual harassment against women – male-dominated hierarchical environments and organizational tolerance of sexual harassment – still prevail in academic medicine. 
Higher-education environments are perceived as permissive environments in part because when targets report sexual harassment, they are retaliated against or there are few consequences for the perpetrator. Academic institutions are replete with cases in which the conduct of offenders is regarded as an open secret, but there are no sanctions for that bad behavior. These offenders often are perceived as superstars in their particular substantive area. Because they hold valued grants or national status within their specialty area, they often receive preferential treatment and are not held accountable for gender-biased and sexually harassing behavior. Interview data regarding sexual harassment in academic medicine reveals that interview respondents and other colleagues often know which individuals have a history of sexually harassing behavior. Both men and women warn colleagues of these perpetrators – knowing that calling out or reporting these behaviors is fruitless – and that the best manner for dealing with their behavior is to avoid or ignore it. This normalization of sexual harassment and gender bias was noted, unfortunately, to fuel similar behavior in new cohorts of medicine faculty.1 
Sexual harassment of women in academic medicine starts in medical school. Female medical students are significantly more likely to experience sexual harassment by faculty and staff than are graduate or undergraduate students. Sexual harassment continues into residency training with residency described as “breeding grounds for abusive behavior by superiors.”1 Interview studies report that both men and women trainees widely accept harassing behavior at this stage of their training. The expectation of abusive and grueling conditions during residency caused several respondents to view sexual harassment as part of a continuum that they were expected to endure. Female residents in surgery and emergency medicine are more likely to be harassed than those in other specialties because of the high value placed on a hierarchical and authoritative workplace. Once out of residency, the sexual harassment of women in the workplace continues. A recent meta-analysis reveals that 58% of women faculty experience sexual harassment at work. Academic medicine has the second-highest rate of sexual harassment, behind the military (69%), as compared with all other workplaces. Women physicians of color experience more harassment (as a combination of sexual and racial harassment) than do white women physicians.1 

Why Women Are Not Likely to Report Sexual Harassment
Only 25% of targets file formal reports with their employer, with even fewer taking claims to court. These numbers are even lower for women in the military and academic medicine, where formal reporting is the last resort for the victims. The reluctance to use formal reporting mechanisms is rooted in the “fear of blame, disbelief, inaction, retaliation, humiliation, ostracism, and the damage to one’s career and reputation.”1 Targets may perceive that there seem to be few benefits and high costs for reporting. Women and nonwhites often resist calling bad behavior “discrimination” because that increases their loss of control and victimhood.1 Women frequently perceive that grievance procedures favor the institution over the individual, and research has proven that women face retaliation, both professional and social, for speaking out. Furthermore, stark power differentials between the target and the perpetrator exacerbate the reluctance to report and the fear of retaliation. The overall effects can be long lasting. 

References:
1. National Academies of Sciences, Engineering, and Medicine. Sexual Harassment of Women: Climate, Culture, and Consequences in Academic Sciences, Engineering, and Medicine. The National Academies Press, Washington, DC; 2018. doi. 10.17226/24994.
2. Choo EK et al. From #MeToo to #TimesUp in Health Care: Can a Culture of Accountability End Inequity and Harassment? Lancet. 2019 Feb 9;393(10171):499-502.
3. Choo EK et al. Time’s Up for Medicine? Only Time Will Tell. N Engl J Med. 2018 Oct 25;379(17):1592-3.
4. Medicine Has Its Own #MeToo Problems. Can Time’s Up Healthcare Fix It? 

Dr. Mitchell is a vascular surgeon at Salem (Ore.) Hospital; Dr. Drudi is as vascular surgery resident at McGill University, Montreal; Dr. Brown is a professor of surgery at the Medical College of Wisconsin. Milwaukee; Dr. Sachdev-Ost is an associate professor of surgery at the University of Pittsburgh Medical Center.

PART I
Reports of sexual harassment and gender discrimination have dominated news headlines, and the #MeToo movement has brought the scope and severity of discriminatory behavior to the forefront of public consciousness. The #MeToo movement has raised national and global awareness of gender discrimination and sexual harassment in all industries and has given rise to Time’s Up initiative within health care.
Academic medicine has not been immune to workplace gender discrimination and sexual harassment as has been vastly reported in the literature and clearly documented in the 2018 National Academies of Sciences, Engineering, and Medicine report, which points out that … “the cumulative effect of sexual harassment is a significant and costly loss of talent in academic science, engineering, and medicine, which has consequences for advancing the nation’s economic and social well-being and its overall public health.”1 
With the increasing recognition that healthcare is an environment especially prone to inequality, gender discrimination and sexual discrimination, the Time’s Up national organization, supported by the Time’s Up Legal Defense Fund, launched the Time’s Up initiative for health care workers on March 1, 2019.2,3 The overarching goal of this initiative is to expose workplace inequalities; drive policy and legislative changes focused on equal pay, equal opportunity, and equal work environments; and support safe, fair, and dignified work for women in health care. 2,3
This article, presented over the next three issues of Vascular Specialist, will present data on the ongoing problem of sexual harassment in medicine, discuss why the problem is prevalent in academic medicine, and provide recommendations for mitigating the problem in our workplace.

Defining & Measuring Sexual Harassment
Although commonly referred to as “sex discrimination,” sexual harassment differs from sexual discrimination. Sex discrimination refers to an employees’ denial of civil rights, raises, job opportunities, employment or a demotion or other mistreatments based on sex. On the other hand, sexual harassment relates to behavior that is inappropriate or offensive. A 2018 report from the National Academies Press defined sexual harassment (a form of discrimination) as comprising three categories of behavior: gender harassment – verbal and nonverbal behaviors that convey hostility, objectification, exclusion, or second-class status about members of one sex; unwanted sexual attention – verbal or physical unwelcome sexual advances, which can include assault; and sexual coercion – when favorable professional or educational treatment is conditional based on sexual activity.1
During 1995-2016, more than 7,000 health care service employees filed claims of sexual harassment with the Equal Employment Opportunity Commission. While this number may seem large, the number of official reports severely undervalues the prevalence of sexual discrimination in U.S. health care.1 Prevalence is best determined using representative validated surveys that rely on firsthand experience or observation of the behavior(s) without requiring the respondent to label those behaviors.

Environments at Risk for Sexual Harassment 
Research reveals that academic settings in the fields of science exhibit characteristics that create high levels of risk for sexual harassment to occur. These environments historically are male dominated, tolerate sexually harassing behavior, and create a hierarchy in which men hold most of the positions of power and authority. Moreover, dependent relationships often exist between these gatekeepers and those subordinate to them, with gatekeepers directly influencing the career advancement of those subordinates.1
The greatest predictor of sexual harassment in the workplace is the organizational climate, which refers to the tolerance for sexual harassment and is measured on three elements: a lack of sanctions against offenders; a perceived risk to those who report sexually harassing behavior; and the perception that one’s report of sexually harassing behavior will not be taken seriously.1 Women are less likely to be directly harassed in environments that do not tolerate harassing behaviors or have a strong, clear, transparent consequence for these behaviors.  

Sexual Harassment in Academic Medicine
Academic medicine has the highest rate of gender and sexual harassment in the health care industry, with about 50% of female academic physicians reporting incidents of sexual harassment.1 A recent survey suggests that more than half (58%) of women surgeons experienced sexual harassment within just the previous year alone.4 The conditions that increase the risk of sexual harassment against women – male-dominated hierarchical environments and organizational tolerance of sexual harassment – still prevail in academic medicine. 
Higher-education environments are perceived as permissive environments in part because when targets report sexual harassment, they are retaliated against or there are few consequences for the perpetrator. Academic institutions are replete with cases in which the conduct of offenders is regarded as an open secret, but there are no sanctions for that bad behavior. These offenders often are perceived as superstars in their particular substantive area. Because they hold valued grants or national status within their specialty area, they often receive preferential treatment and are not held accountable for gender-biased and sexually harassing behavior. Interview data regarding sexual harassment in academic medicine reveals that interview respondents and other colleagues often know which individuals have a history of sexually harassing behavior. Both men and women warn colleagues of these perpetrators – knowing that calling out or reporting these behaviors is fruitless – and that the best manner for dealing with their behavior is to avoid or ignore it. This normalization of sexual harassment and gender bias was noted, unfortunately, to fuel similar behavior in new cohorts of medicine faculty.1 
Sexual harassment of women in academic medicine starts in medical school. Female medical students are significantly more likely to experience sexual harassment by faculty and staff than are graduate or undergraduate students. Sexual harassment continues into residency training with residency described as “breeding grounds for abusive behavior by superiors.”1 Interview studies report that both men and women trainees widely accept harassing behavior at this stage of their training. The expectation of abusive and grueling conditions during residency caused several respondents to view sexual harassment as part of a continuum that they were expected to endure. Female residents in surgery and emergency medicine are more likely to be harassed than those in other specialties because of the high value placed on a hierarchical and authoritative workplace. Once out of residency, the sexual harassment of women in the workplace continues. A recent meta-analysis reveals that 58% of women faculty experience sexual harassment at work. Academic medicine has the second-highest rate of sexual harassment, behind the military (69%), as compared with all other workplaces. Women physicians of color experience more harassment (as a combination of sexual and racial harassment) than do white women physicians.1 

Why Women Are Not Likely to Report Sexual Harassment
Only 25% of targets file formal reports with their employer, with even fewer taking claims to court. These numbers are even lower for women in the military and academic medicine, where formal reporting is the last resort for the victims. The reluctance to use formal reporting mechanisms is rooted in the “fear of blame, disbelief, inaction, retaliation, humiliation, ostracism, and the damage to one’s career and reputation.”1 Targets may perceive that there seem to be few benefits and high costs for reporting. Women and nonwhites often resist calling bad behavior “discrimination” because that increases their loss of control and victimhood.1 Women frequently perceive that grievance procedures favor the institution over the individual, and research has proven that women face retaliation, both professional and social, for speaking out. Furthermore, stark power differentials between the target and the perpetrator exacerbate the reluctance to report and the fear of retaliation. The overall effects can be long lasting. 

References:
1. National Academies of Sciences, Engineering, and Medicine. Sexual Harassment of Women: Climate, Culture, and Consequences in Academic Sciences, Engineering, and Medicine. The National Academies Press, Washington, DC; 2018. doi. 10.17226/24994.
2. Choo EK et al. From #MeToo to #TimesUp in Health Care: Can a Culture of Accountability End Inequity and Harassment? Lancet. 2019 Feb 9;393(10171):499-502.
3. Choo EK et al. Time’s Up for Medicine? Only Time Will Tell. N Engl J Med. 2018 Oct 25;379(17):1592-3.
4. Medicine Has Its Own #MeToo Problems. Can Time’s Up Healthcare Fix It? 

Dr. Mitchell is a vascular surgeon at Salem (Ore.) Hospital; Dr. Drudi is as vascular surgery resident at McGill University, Montreal; Dr. Brown is a professor of surgery at the Medical College of Wisconsin. Milwaukee; Dr. Sachdev-Ost is an associate professor of surgery at the University of Pittsburgh Medical Center.

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FRAX with BMD may not be accurate for women with diabetes

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The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

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In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.

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The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

©wildpixel/Thinkstock

In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.

 

The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

©wildpixel/Thinkstock

In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.

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Cancer survivors face more age-related deficits

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Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

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Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

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USPSTF expands BRCA1/2 testing recommendations

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The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.

Christian Jasiuk/Thinkstock

In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.

The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).

“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.

Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.

By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.

Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.

Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
 

Important step forward

Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.

“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.

While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.

“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.

Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
 

More research needed

Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.

 

 

Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.

“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.

In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.

“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.

Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.

Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
 

Treatment implications

While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH

Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.

The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.

“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
 

Addressing disparities in care

The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.

“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.

Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.

Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.

“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.

The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
 

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The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.

Christian Jasiuk/Thinkstock

In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.

The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).

“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.

Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.

By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.

Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.

Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
 

Important step forward

Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.

“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.

While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.

“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.

Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
 

More research needed

Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.

 

 

Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.

“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.

In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.

“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.

Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.

Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
 

Treatment implications

While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH

Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.

The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.

“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
 

Addressing disparities in care

The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.

“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.

Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.

Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.

“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.

The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
 

 

The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.

Christian Jasiuk/Thinkstock

In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.

The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).

“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.

Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.

By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.

Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.

Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
 

Important step forward

Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.

“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.

While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.

“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.

Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
 

More research needed

Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.

 

 

Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.

“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.

In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.

“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.

Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.

Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
 

Treatment implications

While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH

Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.

The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.

“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
 

Addressing disparities in care

The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.

“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.

Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.

Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.

“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.

The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
 

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Self-reported falls can predict osteoporotic fracture risk

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A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

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In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

Body

Fragility fractures remain a major contributor to morbidity and even mortality of aging populations. Concerted efforts of clinicians, epidemiologists, and researchers have yielded an assortment of diagnostic strategies and prognostic algorithms in efforts to identify individuals at fracture risk. A variety of demographic (age, sex), biological (family history, specific disorders and medications), anatomical (bone mineral density, body mass index), and behavioral (smoking, alcohol consumption) parameters are recognized as predictors of fracture risk, and often are incorporated in predictive algorithms for fracture predisposition. FRAX (Fracture Risk Assessment) is a widely used screening tool that is valid in offering fracture risk quantification across populations (Arch Osteoporos. 2016 Dec;11[1]:25; World Health Organization Assessment of Osteoporosis at the Primary Health Care Level).

 
Aging and accompanying neurocognitive deterioration, visual impairment, as well as iatrogenic factors are recognized to contribute to predisposition to falls in aging populations. A propensity for falls has long been regarded as a fracture risk (Curr Osteoporos Rep. 2008;6[4]:149-54). However, the evidence to support this logical assumption has been mixed with resulting exclusion of tendency to fall from commonly utilized fracture risk predictive models and tools. A predisposition to and frequency of falls is considered neither a risk modulator nor a mediator in the commonly utilized FRAX-based fracture risk assessments, and it is believed that fracture probability may be underestimated by FRAX in those predisposed to frequent falls (J Clin Densitom. 2011 Jul-Sep;14[3]:194–204).

 
The landscape of fracture risk assessment and quantification in the aforementioned backdrop has been refreshingly enhanced by a recent contribution by Leslie et al. wherein the authors provide real-life evidence relating self-reported falls to fracture risk. In a robust population sample nearing 25,000 women, increasing number of falls within the past year was associated with an increasing fracture risk, and this relationship persisted after adjusting for covariates that are recognized to predispose to fragility fractures, including age, body mass index, and bone mineral density. Women’s health providers are encouraged to familiarize themselves with the work of Leslie et al.; the authors’ message, that fall history be incorporated into risk quantification measures, is striking in its simplicity and profound in its preventative potential given that fall risk in and of itself may be mitigated in many through targeted interventions.

 
Lubna Pal, MBBS, MS, is professor and fellowship director of the division of reproductive endocrinology & infertility at Yale University, New Haven, Conn. She also is the director of the Yale reproductive endocrinology & infertility menopause program. She said she had no relevant financial disclosures. Email her at [email protected].
 

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Body

Fragility fractures remain a major contributor to morbidity and even mortality of aging populations. Concerted efforts of clinicians, epidemiologists, and researchers have yielded an assortment of diagnostic strategies and prognostic algorithms in efforts to identify individuals at fracture risk. A variety of demographic (age, sex), biological (family history, specific disorders and medications), anatomical (bone mineral density, body mass index), and behavioral (smoking, alcohol consumption) parameters are recognized as predictors of fracture risk, and often are incorporated in predictive algorithms for fracture predisposition. FRAX (Fracture Risk Assessment) is a widely used screening tool that is valid in offering fracture risk quantification across populations (Arch Osteoporos. 2016 Dec;11[1]:25; World Health Organization Assessment of Osteoporosis at the Primary Health Care Level).

 
Aging and accompanying neurocognitive deterioration, visual impairment, as well as iatrogenic factors are recognized to contribute to predisposition to falls in aging populations. A propensity for falls has long been regarded as a fracture risk (Curr Osteoporos Rep. 2008;6[4]:149-54). However, the evidence to support this logical assumption has been mixed with resulting exclusion of tendency to fall from commonly utilized fracture risk predictive models and tools. A predisposition to and frequency of falls is considered neither a risk modulator nor a mediator in the commonly utilized FRAX-based fracture risk assessments, and it is believed that fracture probability may be underestimated by FRAX in those predisposed to frequent falls (J Clin Densitom. 2011 Jul-Sep;14[3]:194–204).

 
The landscape of fracture risk assessment and quantification in the aforementioned backdrop has been refreshingly enhanced by a recent contribution by Leslie et al. wherein the authors provide real-life evidence relating self-reported falls to fracture risk. In a robust population sample nearing 25,000 women, increasing number of falls within the past year was associated with an increasing fracture risk, and this relationship persisted after adjusting for covariates that are recognized to predispose to fragility fractures, including age, body mass index, and bone mineral density. Women’s health providers are encouraged to familiarize themselves with the work of Leslie et al.; the authors’ message, that fall history be incorporated into risk quantification measures, is striking in its simplicity and profound in its preventative potential given that fall risk in and of itself may be mitigated in many through targeted interventions.

 
Lubna Pal, MBBS, MS, is professor and fellowship director of the division of reproductive endocrinology & infertility at Yale University, New Haven, Conn. She also is the director of the Yale reproductive endocrinology & infertility menopause program. She said she had no relevant financial disclosures. Email her at [email protected].
 

Body

Fragility fractures remain a major contributor to morbidity and even mortality of aging populations. Concerted efforts of clinicians, epidemiologists, and researchers have yielded an assortment of diagnostic strategies and prognostic algorithms in efforts to identify individuals at fracture risk. A variety of demographic (age, sex), biological (family history, specific disorders and medications), anatomical (bone mineral density, body mass index), and behavioral (smoking, alcohol consumption) parameters are recognized as predictors of fracture risk, and often are incorporated in predictive algorithms for fracture predisposition. FRAX (Fracture Risk Assessment) is a widely used screening tool that is valid in offering fracture risk quantification across populations (Arch Osteoporos. 2016 Dec;11[1]:25; World Health Organization Assessment of Osteoporosis at the Primary Health Care Level).

 
Aging and accompanying neurocognitive deterioration, visual impairment, as well as iatrogenic factors are recognized to contribute to predisposition to falls in aging populations. A propensity for falls has long been regarded as a fracture risk (Curr Osteoporos Rep. 2008;6[4]:149-54). However, the evidence to support this logical assumption has been mixed with resulting exclusion of tendency to fall from commonly utilized fracture risk predictive models and tools. A predisposition to and frequency of falls is considered neither a risk modulator nor a mediator in the commonly utilized FRAX-based fracture risk assessments, and it is believed that fracture probability may be underestimated by FRAX in those predisposed to frequent falls (J Clin Densitom. 2011 Jul-Sep;14[3]:194–204).

 
The landscape of fracture risk assessment and quantification in the aforementioned backdrop has been refreshingly enhanced by a recent contribution by Leslie et al. wherein the authors provide real-life evidence relating self-reported falls to fracture risk. In a robust population sample nearing 25,000 women, increasing number of falls within the past year was associated with an increasing fracture risk, and this relationship persisted after adjusting for covariates that are recognized to predispose to fragility fractures, including age, body mass index, and bone mineral density. Women’s health providers are encouraged to familiarize themselves with the work of Leslie et al.; the authors’ message, that fall history be incorporated into risk quantification measures, is striking in its simplicity and profound in its preventative potential given that fall risk in and of itself may be mitigated in many through targeted interventions.

 
Lubna Pal, MBBS, MS, is professor and fellowship director of the division of reproductive endocrinology & infertility at Yale University, New Haven, Conn. She also is the director of the Yale reproductive endocrinology & infertility menopause program. She said she had no relevant financial disclosures. Email her at [email protected].
 

Title
Do focus on falls when assessing fracture risk
Do focus on falls when assessing fracture risk

A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

Alexander Raths/Fotolia

In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

Alexander Raths/Fotolia

In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

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Planned Parenthood withdraws from Title X

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Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

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Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

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Fluoride exposure during pregnancy tied to lower IQ score in children

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Maternal exposure to fluoride during pregnancy was associated with lower IQ scores in children at 3 years and 4 years, with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.

LightFieldStudios/iStock/Getty Images Plus

“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”

This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.

Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.

Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.

The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).

Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).

Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.

In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.

The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.

Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.

“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”

However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.

“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”

This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.

SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.

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Maternal exposure to fluoride during pregnancy was associated with lower IQ scores in children at 3 years and 4 years, with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.

LightFieldStudios/iStock/Getty Images Plus

“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”

This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.

Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.

Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.

The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).

Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).

Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.

In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.

The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.

Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.

“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”

However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.

“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”

This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.

SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.

 

Maternal exposure to fluoride during pregnancy was associated with lower IQ scores in children at 3 years and 4 years, with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.

LightFieldStudios/iStock/Getty Images Plus

“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”

This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.

Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.

Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.

The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).

Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).

Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.

In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.

The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.

Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.

“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”

However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.

“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”

This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.

SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.

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Aspirin interacts with epigenetics to influence breast cancer mortality

Intersection of breast cancer, epigenetics, and aspirin
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The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

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This study offers new insights into the intersection of epigenetics, prediagnosis aspirin use, and breast cancer survival at a time when there is an urgent need to understand why some women respond differently to treatment and to find cost-effective therapies for the disease.

Epigenetics is a promising avenue of investigation because epigenetic shifts, such as DNA methylation, that impact the genes responsible for cell behavior and DNA damage and repair are known to contribute to and exacerbate cancer. These epigenetic signatures could act as biomarkers for risk in cancer and also aid with more effective treatment approaches. For example, aspirin is known to affect DNA methylation at certain sites in colon cancer, hence this study’s hypothesis that pre–cancer diagnosis aspirin use would interact with epigenetic signatures and influence breast cancer outcomes.
 

Kristen M. C. Malecki, PhD, is from the department of population health sciences in the School of Medicine and Public Health at the University of Wisconsin, Madison. The comments are adapted from an accompanying editorial (Cancer. 2019 Aug 12. doi: 10.1002/cncr.32365). Dr. Malecki declared support from the National Institutes of Health, National Institute for Environmental Health Sciences Breast Cancer, and the Environment Research Program.

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This study offers new insights into the intersection of epigenetics, prediagnosis aspirin use, and breast cancer survival at a time when there is an urgent need to understand why some women respond differently to treatment and to find cost-effective therapies for the disease.

Epigenetics is a promising avenue of investigation because epigenetic shifts, such as DNA methylation, that impact the genes responsible for cell behavior and DNA damage and repair are known to contribute to and exacerbate cancer. These epigenetic signatures could act as biomarkers for risk in cancer and also aid with more effective treatment approaches. For example, aspirin is known to affect DNA methylation at certain sites in colon cancer, hence this study’s hypothesis that pre–cancer diagnosis aspirin use would interact with epigenetic signatures and influence breast cancer outcomes.
 

Kristen M. C. Malecki, PhD, is from the department of population health sciences in the School of Medicine and Public Health at the University of Wisconsin, Madison. The comments are adapted from an accompanying editorial (Cancer. 2019 Aug 12. doi: 10.1002/cncr.32365). Dr. Malecki declared support from the National Institutes of Health, National Institute for Environmental Health Sciences Breast Cancer, and the Environment Research Program.

Body

 

This study offers new insights into the intersection of epigenetics, prediagnosis aspirin use, and breast cancer survival at a time when there is an urgent need to understand why some women respond differently to treatment and to find cost-effective therapies for the disease.

Epigenetics is a promising avenue of investigation because epigenetic shifts, such as DNA methylation, that impact the genes responsible for cell behavior and DNA damage and repair are known to contribute to and exacerbate cancer. These epigenetic signatures could act as biomarkers for risk in cancer and also aid with more effective treatment approaches. For example, aspirin is known to affect DNA methylation at certain sites in colon cancer, hence this study’s hypothesis that pre–cancer diagnosis aspirin use would interact with epigenetic signatures and influence breast cancer outcomes.
 

Kristen M. C. Malecki, PhD, is from the department of population health sciences in the School of Medicine and Public Health at the University of Wisconsin, Madison. The comments are adapted from an accompanying editorial (Cancer. 2019 Aug 12. doi: 10.1002/cncr.32365). Dr. Malecki declared support from the National Institutes of Health, National Institute for Environmental Health Sciences Breast Cancer, and the Environment Research Program.

Title
Intersection of breast cancer, epigenetics, and aspirin
Intersection of breast cancer, epigenetics, and aspirin

 

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

 

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

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PCOS incidence is on the rise, but it remains underdiagnosed and undermanaged

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– The incidence of polycystic ovary syndrome (PCOS) is on the rise, and a nurse practitioner urged her colleagues to give it full attention because of the danger it poses to patients.

“Underdiagnosed and undermanaged, it’s complex and a more serious condition than ever before because of the complications that can occur,” said R. Mimi Secor, DNP, FNP-BC, FAANP, FAAN, who spoke at the Metabolic & Endocrine Disease Summit by Global Academy for Medical Education.

PCOS is the most common reproductive endocrine disorder in the United States, affecting more than 5 million women, or an estimated 6%-10% of the population. Obesity is a risk factor, although lean women account for 10% of cases for reasons that are not understood, according to Dr. Secor, a senior lecturer at Advanced Practice Education Associates in Onset, Mass. In addition, the condition is linked to many sequelae, including multiple sclerosis, diabetes, cardiovascular disease, infertility, mental health problems, and cancer, she said.

Dr. Secor offered these pearls about PCOS:

  • Understand the predictive value of oligomenorrhea (infrequent menstrual periods) as a sign of PCOS. “If you’re working in a low-income clinic, you can do well to make a diagnosis without a lot of expensive tests,” she said.
  • Urge women with PCOS to get pregnant early if they want to have children. “Infertility is a big problem [among these women],” she said. “They shouldn’t wait until they’re 35 to have babies. They should have them in their 20s.”
  • Use insulin control as a tool. “Insulin stimulates ovarian production of testosterone. If we can manage patients around insulin, that can be very helpful.” Losing just 5% of body weight can make a difference in insulin control, Dr. Secor said. “Go for a small change, and help [the patient] maintain that.”
  • Monitor patients carefully for cancer. Women who don’t ovulate regularly on a monthly basis face a higher risk of uterine cancer, compared with women who ovulate monthly, she said, and tumors can develop with few symptoms. “If [there is] one drop of bleeding more than a year after menopause,” you need to get a mandatory workup to make sure the patient doesn’t have uterine cancer. Biopsy remains the “gold standard” as a diagnostic tool, she reminded attendees.
  • Watch for mental health conditions, especially anxiety, in patients with PCOS. “They seem to be wired for anxiety, and they need a lot of emotional support,” Dr. Secor said.
  • Hormonal contraceptives can be safe and effective as a treatment for PCOS in women who don’t wish to become pregnant, she said. But be aware that combination contraceptive drugs can affect women emotionally.

Global Academy and this news organization are owned by the same parent company. Dr. Secor disclosed speaker relationships with Duchesnay and Osphena.

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– The incidence of polycystic ovary syndrome (PCOS) is on the rise, and a nurse practitioner urged her colleagues to give it full attention because of the danger it poses to patients.

“Underdiagnosed and undermanaged, it’s complex and a more serious condition than ever before because of the complications that can occur,” said R. Mimi Secor, DNP, FNP-BC, FAANP, FAAN, who spoke at the Metabolic & Endocrine Disease Summit by Global Academy for Medical Education.

PCOS is the most common reproductive endocrine disorder in the United States, affecting more than 5 million women, or an estimated 6%-10% of the population. Obesity is a risk factor, although lean women account for 10% of cases for reasons that are not understood, according to Dr. Secor, a senior lecturer at Advanced Practice Education Associates in Onset, Mass. In addition, the condition is linked to many sequelae, including multiple sclerosis, diabetes, cardiovascular disease, infertility, mental health problems, and cancer, she said.

Dr. Secor offered these pearls about PCOS:

  • Understand the predictive value of oligomenorrhea (infrequent menstrual periods) as a sign of PCOS. “If you’re working in a low-income clinic, you can do well to make a diagnosis without a lot of expensive tests,” she said.
  • Urge women with PCOS to get pregnant early if they want to have children. “Infertility is a big problem [among these women],” she said. “They shouldn’t wait until they’re 35 to have babies. They should have them in their 20s.”
  • Use insulin control as a tool. “Insulin stimulates ovarian production of testosterone. If we can manage patients around insulin, that can be very helpful.” Losing just 5% of body weight can make a difference in insulin control, Dr. Secor said. “Go for a small change, and help [the patient] maintain that.”
  • Monitor patients carefully for cancer. Women who don’t ovulate regularly on a monthly basis face a higher risk of uterine cancer, compared with women who ovulate monthly, she said, and tumors can develop with few symptoms. “If [there is] one drop of bleeding more than a year after menopause,” you need to get a mandatory workup to make sure the patient doesn’t have uterine cancer. Biopsy remains the “gold standard” as a diagnostic tool, she reminded attendees.
  • Watch for mental health conditions, especially anxiety, in patients with PCOS. “They seem to be wired for anxiety, and they need a lot of emotional support,” Dr. Secor said.
  • Hormonal contraceptives can be safe and effective as a treatment for PCOS in women who don’t wish to become pregnant, she said. But be aware that combination contraceptive drugs can affect women emotionally.

Global Academy and this news organization are owned by the same parent company. Dr. Secor disclosed speaker relationships with Duchesnay and Osphena.

– The incidence of polycystic ovary syndrome (PCOS) is on the rise, and a nurse practitioner urged her colleagues to give it full attention because of the danger it poses to patients.

“Underdiagnosed and undermanaged, it’s complex and a more serious condition than ever before because of the complications that can occur,” said R. Mimi Secor, DNP, FNP-BC, FAANP, FAAN, who spoke at the Metabolic & Endocrine Disease Summit by Global Academy for Medical Education.

PCOS is the most common reproductive endocrine disorder in the United States, affecting more than 5 million women, or an estimated 6%-10% of the population. Obesity is a risk factor, although lean women account for 10% of cases for reasons that are not understood, according to Dr. Secor, a senior lecturer at Advanced Practice Education Associates in Onset, Mass. In addition, the condition is linked to many sequelae, including multiple sclerosis, diabetes, cardiovascular disease, infertility, mental health problems, and cancer, she said.

Dr. Secor offered these pearls about PCOS:

  • Understand the predictive value of oligomenorrhea (infrequent menstrual periods) as a sign of PCOS. “If you’re working in a low-income clinic, you can do well to make a diagnosis without a lot of expensive tests,” she said.
  • Urge women with PCOS to get pregnant early if they want to have children. “Infertility is a big problem [among these women],” she said. “They shouldn’t wait until they’re 35 to have babies. They should have them in their 20s.”
  • Use insulin control as a tool. “Insulin stimulates ovarian production of testosterone. If we can manage patients around insulin, that can be very helpful.” Losing just 5% of body weight can make a difference in insulin control, Dr. Secor said. “Go for a small change, and help [the patient] maintain that.”
  • Monitor patients carefully for cancer. Women who don’t ovulate regularly on a monthly basis face a higher risk of uterine cancer, compared with women who ovulate monthly, she said, and tumors can develop with few symptoms. “If [there is] one drop of bleeding more than a year after menopause,” you need to get a mandatory workup to make sure the patient doesn’t have uterine cancer. Biopsy remains the “gold standard” as a diagnostic tool, she reminded attendees.
  • Watch for mental health conditions, especially anxiety, in patients with PCOS. “They seem to be wired for anxiety, and they need a lot of emotional support,” Dr. Secor said.
  • Hormonal contraceptives can be safe and effective as a treatment for PCOS in women who don’t wish to become pregnant, she said. But be aware that combination contraceptive drugs can affect women emotionally.

Global Academy and this news organization are owned by the same parent company. Dr. Secor disclosed speaker relationships with Duchesnay and Osphena.

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Click for Credit: Predicting preeclampsia; MI & stroke post-cancer Dx; more

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Here are 5 articles from the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Smoking cessation could delay or prevent rheumatoid arthritis

To take the posttest, go to: https://bit.ly/2YguN2r
Expires February 22, 2020

2. No increased pregnancy loss risk for women conceiving soon after stillbirth

To take the posttest, go to: https://bit.ly/2ZnMaLc
Expires March 4, 2020

3. Total plasma tau correlates with dementia onset, Alzheimer’s disease

To take the posttest, go to: https://bit.ly/2YeglYV
Expires March 9, 2020

4. MI, strokes spike during 30 days after cancer diagnosis

To take the posttest, go to: https://bit.ly/2GCKZAv
Expires March 12, 2020

5. Combination model predicts imminent preeclampsia

To take the posttest, go to: https://bit.ly/2LTohrO
Expires February 21, 2020

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Here are 5 articles from the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Smoking cessation could delay or prevent rheumatoid arthritis

To take the posttest, go to: https://bit.ly/2YguN2r
Expires February 22, 2020

2. No increased pregnancy loss risk for women conceiving soon after stillbirth

To take the posttest, go to: https://bit.ly/2ZnMaLc
Expires March 4, 2020

3. Total plasma tau correlates with dementia onset, Alzheimer’s disease

To take the posttest, go to: https://bit.ly/2YeglYV
Expires March 9, 2020

4. MI, strokes spike during 30 days after cancer diagnosis

To take the posttest, go to: https://bit.ly/2GCKZAv
Expires March 12, 2020

5. Combination model predicts imminent preeclampsia

To take the posttest, go to: https://bit.ly/2LTohrO
Expires February 21, 2020

Here are 5 articles from the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Smoking cessation could delay or prevent rheumatoid arthritis

To take the posttest, go to: https://bit.ly/2YguN2r
Expires February 22, 2020

2. No increased pregnancy loss risk for women conceiving soon after stillbirth

To take the posttest, go to: https://bit.ly/2ZnMaLc
Expires March 4, 2020

3. Total plasma tau correlates with dementia onset, Alzheimer’s disease

To take the posttest, go to: https://bit.ly/2YeglYV
Expires March 9, 2020

4. MI, strokes spike during 30 days after cancer diagnosis

To take the posttest, go to: https://bit.ly/2GCKZAv
Expires March 12, 2020

5. Combination model predicts imminent preeclampsia

To take the posttest, go to: https://bit.ly/2LTohrO
Expires February 21, 2020

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Clinician Reviews - 29(8)
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