Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Among older adults with low and intermediate genetic risk for dementia, favorable modifiable health and lifestyle factors are associated with lower likelihood of dementia. But among people at high genetic risk for dementia, these potentially modifiable factors – not smoking, not having depression or diabetes, getting regular physical activity, avoiding social isolation, and following a healthy diet – may not have protective associations, according to research published in Nature Medicine.

Recent analyses have indicated that eliminating known modifiable risk factors for dementia at a population level could prevent one-third of dementia cases, but prevention trials “have yielded inconsistent results so far,” wrote first author Silvan Licher, MD, of the department of epidemiology at Erasmus University Medical Center Rotterdam (the Netherlands) and his colleagues.

“Prior studies have mostly focused on the risk of dementia associated with an individual protective factor, yet the combination of multiple factors may yield more beneficial effects than the individual parts,” they wrote. “Combining data about a number of factors is also important because it takes into account the multifactorial nature of late-life dementia. We used data from the Rotterdam Study to determine to what extent a favorable profile based on modifiable risk factors is associated with a lower risk of dementia among individuals at low, intermediate, or high genetic risk.”

Grouped by APOE genotype

Patients who were apolipoprotein E epsilon-4 allele (APOE4) carriers (i.e., APOE2 and 4, APOE3 and 4, or two APOE4) were classified as having high genetic risk (n = 1,747). Other APOE genotypes were considered intermediate risk (n = 3,718 with two APOE3 alleles) or low risk (n = 887 with either two APOE2 alleles or APOE2 and 3).

The researchers measured six potentially modifiable lifestyle or health factors that “have been implicated in a lower risk of dementia.” Modifiable risk scores ranged from 0 to 6. Participants were classified as having an unfavorable profile (0-2 protective factors), an intermediate profile (3-4 protective factors), or a favorable profile (5-6 factors).

The researchers calculated the relative risk of developing dementia using a Cox proportional hazards model and the absolutely risk using competing risk models.

In all, 56.2% of the participants were women, the average age was about 69 years, and patient characteristics were similar across the categories of APOE risk. APOE4 carriers received dementia diagnoses at a younger age, more often had a parental history of dementia, and had higher total cholesterol levels, compared with noncarriers. In all, 915 people received a dementia diagnosis, of whom 739 received a diagnosis of Alzheimer’s disease. The other 2,644 participants died free from dementia. The median follow-up was 14.1 years.

“Dementia risk was significantly higher among participants at high or intermediate APOE risk, compared with those at low APOE risk,” the researchers said. In addition, the risk of dementia increased in participants who had fewer protective factors. Those with 0-2 protective factors had a 29% higher risk of dementia, compared with participants with 5 or 6 protective factors, after adjusting for age, sex, level of education, parental history of dementia, history of stroke, systolic blood pressure, and total and high-density lipoprotein cholesterol.

Lifestyle benefits tended to be greater in younger participants

“APOE genotype significantly modified the association between protective factors and dementia,” the authors said. Compared with participants with protective modifiable risk profiles, participants with unfavorable modifiable risk profiles had greater risk for dementia in the low–APOE risk group (hazard ratio, 2.51) and intermediate–APOE risk group (HR, 1.39), but not in the high–APOE risk group.

“Protective associations of favorable risk profiles against dementia tended to be stronger in younger individuals than in older individuals and were most pronounced for younger individuals at low APOE risk,” Dr. Licher and colleagues said. In a sensitivity analysis that used a polygenic risk score for Alzheimer’s disease based on 27 variants other than APOE to determine participants’ genetic risk, the patterns were “attenuated yet largely comparable,” they wrote. Patterns also remained consistent when the researchers used an ideal cardiovascular health score to indicate modifiable health profiles.

“Our results confirm that individuals with a favorable profile have a lower risk of dementia than those with intermediate or unfavorable profiles based on modifiable risk factors,” they said. Unlike in a subgroup analysis of data from the FINGER study, however, “this study found that a favorable profile could not offset high APOE risk.”

The findings may have implications for clinical trial design and suggest that APOE4 carriers may need to be targeted earlier in the disease process to influence their risk for dementia.

“On the positive side, results from this study show that avoiding an unhealthy lifestyle could potentially prevent or postpone the onset of dementia in most individuals in the population (73%), namely those at low and intermediate genetic risk,” the investigators wrote. “Among these, the majority were categorized has having a favorable profile (66%), yet room for improvement is still substantial.”

The study lacked data on hearing impairment and did not capture shifts to more adverse or optimal lifestyles during follow-up. In addition, the results are based on relatively small samples in each risk category, and the estimates had wide confidence intervals. The population was older and mostly of European descent, which limits the generalizability of the findings, the authors noted.

Lifestyle factors may benefit only people with low genetic risk

“The authors’ key finding was that modifiable lifestyle risk factors were able to reduce dementia risk only in people who did not have an APOE4 allele and hence were at lower genetic risk,” said Kenneth Rockwood, MD, professor of geriatric medicine and neurology at Dalhousie University in Halifax, N.S., and his coauthors, in an accompanying editorial.

The findings contrast with those of another recent population-based study using data from the UK Biobank (JAMA. 2019;322[5]:430-7. doi: 10.1001/jama.2019.9879), which suggested that modifiable factors affect dementia risk regardless of genetic risk.

Together, these studies “tell us that ... we must better understand outcomes in those most at risk,” they said. “We might begin by recognizing that aging is essential, rather than incidental, to dementia disease expression.” Future research should focus on people living with frailty, who often are excluded from trials and are at high risk for dementia. Older adults who develop delirium also may be an ideal target group of patients at increased risk for dementia.

“Reducing the extent of disease expression in people prone to developing dementia late in life is difficult. Studies investigating whether dementia can be prevented at all, such as the Rotterdam study, and then whether it can be prevented in the people at greatest risk, can be commended for their clear-eyed approach,” Dr. Rockwood and colleagues said.

The Rotterdam Study is funded by Erasmus Medical Center and University, as well as a variety of Dutch organizations, institutes, and government ministries, and the European Commission. The authors had no competing interests.

Dr. Rockwood is president and chief science officer of DGI Clinical, which has contracts with pharmaceutical and device manufacturers related to individualized outcome measurement.

[email protected]

SOURCES: Licher S et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0547-7; and Rockwood K et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0575-3.

Among older adults with low and intermediate genetic risk for dementia, favorable modifiable health and lifestyle factors are associated with lower likelihood of dementia. But among people at high genetic risk for dementia, these potentially modifiable factors – not smoking, not having depression or diabetes, getting regular physical activity, avoiding social isolation, and following a healthy diet – may not have protective associations, according to research published in Nature Medicine.

Recent analyses have indicated that eliminating known modifiable risk factors for dementia at a population level could prevent one-third of dementia cases, but prevention trials “have yielded inconsistent results so far,” wrote first author Silvan Licher, MD, of the department of epidemiology at Erasmus University Medical Center Rotterdam (the Netherlands) and his colleagues.

“Prior studies have mostly focused on the risk of dementia associated with an individual protective factor, yet the combination of multiple factors may yield more beneficial effects than the individual parts,” they wrote. “Combining data about a number of factors is also important because it takes into account the multifactorial nature of late-life dementia. We used data from the Rotterdam Study to determine to what extent a favorable profile based on modifiable risk factors is associated with a lower risk of dementia among individuals at low, intermediate, or high genetic risk.”

Grouped by APOE genotype

Patients who were apolipoprotein E epsilon-4 allele (APOE4) carriers (i.e., APOE2 and 4, APOE3 and 4, or two APOE4) were classified as having high genetic risk (n = 1,747). Other APOE genotypes were considered intermediate risk (n = 3,718 with two APOE3 alleles) or low risk (n = 887 with either two APOE2 alleles or APOE2 and 3).

The researchers measured six potentially modifiable lifestyle or health factors that “have been implicated in a lower risk of dementia.” Modifiable risk scores ranged from 0 to 6. Participants were classified as having an unfavorable profile (0-2 protective factors), an intermediate profile (3-4 protective factors), or a favorable profile (5-6 factors).

The researchers calculated the relative risk of developing dementia using a Cox proportional hazards model and the absolutely risk using competing risk models.

In all, 56.2% of the participants were women, the average age was about 69 years, and patient characteristics were similar across the categories of APOE risk. APOE4 carriers received dementia diagnoses at a younger age, more often had a parental history of dementia, and had higher total cholesterol levels, compared with noncarriers. In all, 915 people received a dementia diagnosis, of whom 739 received a diagnosis of Alzheimer’s disease. The other 2,644 participants died free from dementia. The median follow-up was 14.1 years.

“Dementia risk was significantly higher among participants at high or intermediate APOE risk, compared with those at low APOE risk,” the researchers said. In addition, the risk of dementia increased in participants who had fewer protective factors. Those with 0-2 protective factors had a 29% higher risk of dementia, compared with participants with 5 or 6 protective factors, after adjusting for age, sex, level of education, parental history of dementia, history of stroke, systolic blood pressure, and total and high-density lipoprotein cholesterol.

Lifestyle benefits tended to be greater in younger participants

“APOE genotype significantly modified the association between protective factors and dementia,” the authors said. Compared with participants with protective modifiable risk profiles, participants with unfavorable modifiable risk profiles had greater risk for dementia in the low–APOE risk group (hazard ratio, 2.51) and intermediate–APOE risk group (HR, 1.39), but not in the high–APOE risk group.

“Protective associations of favorable risk profiles against dementia tended to be stronger in younger individuals than in older individuals and were most pronounced for younger individuals at low APOE risk,” Dr. Licher and colleagues said. In a sensitivity analysis that used a polygenic risk score for Alzheimer’s disease based on 27 variants other than APOE to determine participants’ genetic risk, the patterns were “attenuated yet largely comparable,” they wrote. Patterns also remained consistent when the researchers used an ideal cardiovascular health score to indicate modifiable health profiles.

“Our results confirm that individuals with a favorable profile have a lower risk of dementia than those with intermediate or unfavorable profiles based on modifiable risk factors,” they said. Unlike in a subgroup analysis of data from the FINGER study, however, “this study found that a favorable profile could not offset high APOE risk.”

The findings may have implications for clinical trial design and suggest that APOE4 carriers may need to be targeted earlier in the disease process to influence their risk for dementia.

“On the positive side, results from this study show that avoiding an unhealthy lifestyle could potentially prevent or postpone the onset of dementia in most individuals in the population (73%), namely those at low and intermediate genetic risk,” the investigators wrote. “Among these, the majority were categorized has having a favorable profile (66%), yet room for improvement is still substantial.”

The study lacked data on hearing impairment and did not capture shifts to more adverse or optimal lifestyles during follow-up. In addition, the results are based on relatively small samples in each risk category, and the estimates had wide confidence intervals. The population was older and mostly of European descent, which limits the generalizability of the findings, the authors noted.

Lifestyle factors may benefit only people with low genetic risk

“The authors’ key finding was that modifiable lifestyle risk factors were able to reduce dementia risk only in people who did not have an APOE4 allele and hence were at lower genetic risk,” said Kenneth Rockwood, MD, professor of geriatric medicine and neurology at Dalhousie University in Halifax, N.S., and his coauthors, in an accompanying editorial.

The findings contrast with those of another recent population-based study using data from the UK Biobank (JAMA. 2019;322[5]:430-7. doi: 10.1001/jama.2019.9879), which suggested that modifiable factors affect dementia risk regardless of genetic risk.

Together, these studies “tell us that ... we must better understand outcomes in those most at risk,” they said. “We might begin by recognizing that aging is essential, rather than incidental, to dementia disease expression.” Future research should focus on people living with frailty, who often are excluded from trials and are at high risk for dementia. Older adults who develop delirium also may be an ideal target group of patients at increased risk for dementia.

“Reducing the extent of disease expression in people prone to developing dementia late in life is difficult. Studies investigating whether dementia can be prevented at all, such as the Rotterdam study, and then whether it can be prevented in the people at greatest risk, can be commended for their clear-eyed approach,” Dr. Rockwood and colleagues said.

The Rotterdam Study is funded by Erasmus Medical Center and University, as well as a variety of Dutch organizations, institutes, and government ministries, and the European Commission. The authors had no competing interests.

Dr. Rockwood is president and chief science officer of DGI Clinical, which has contracts with pharmaceutical and device manufacturers related to individualized outcome measurement.

[email protected]

SOURCES: Licher S et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0547-7; and Rockwood K et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0575-3.

Among older adults with low and intermediate genetic risk for dementia, favorable modifiable health and lifestyle factors are associated with lower likelihood of dementia. But among people at high genetic risk for dementia, these potentially modifiable factors – not smoking, not having depression or diabetes, getting regular physical activity, avoiding social isolation, and following a healthy diet – may not have protective associations, according to research published in Nature Medicine.

Recent analyses have indicated that eliminating known modifiable risk factors for dementia at a population level could prevent one-third of dementia cases, but prevention trials “have yielded inconsistent results so far,” wrote first author Silvan Licher, MD, of the department of epidemiology at Erasmus University Medical Center Rotterdam (the Netherlands) and his colleagues.

“Prior studies have mostly focused on the risk of dementia associated with an individual protective factor, yet the combination of multiple factors may yield more beneficial effects than the individual parts,” they wrote. “Combining data about a number of factors is also important because it takes into account the multifactorial nature of late-life dementia. We used data from the Rotterdam Study to determine to what extent a favorable profile based on modifiable risk factors is associated with a lower risk of dementia among individuals at low, intermediate, or high genetic risk.”

Grouped by APOE genotype

Patients who were apolipoprotein E epsilon-4 allele (APOE4) carriers (i.e., APOE2 and 4, APOE3 and 4, or two APOE4) were classified as having high genetic risk (n = 1,747). Other APOE genotypes were considered intermediate risk (n = 3,718 with two APOE3 alleles) or low risk (n = 887 with either two APOE2 alleles or APOE2 and 3).

The researchers measured six potentially modifiable lifestyle or health factors that “have been implicated in a lower risk of dementia.” Modifiable risk scores ranged from 0 to 6. Participants were classified as having an unfavorable profile (0-2 protective factors), an intermediate profile (3-4 protective factors), or a favorable profile (5-6 factors).

The researchers calculated the relative risk of developing dementia using a Cox proportional hazards model and the absolutely risk using competing risk models.

In all, 56.2% of the participants were women, the average age was about 69 years, and patient characteristics were similar across the categories of APOE risk. APOE4 carriers received dementia diagnoses at a younger age, more often had a parental history of dementia, and had higher total cholesterol levels, compared with noncarriers. In all, 915 people received a dementia diagnosis, of whom 739 received a diagnosis of Alzheimer’s disease. The other 2,644 participants died free from dementia. The median follow-up was 14.1 years.

“Dementia risk was significantly higher among participants at high or intermediate APOE risk, compared with those at low APOE risk,” the researchers said. In addition, the risk of dementia increased in participants who had fewer protective factors. Those with 0-2 protective factors had a 29% higher risk of dementia, compared with participants with 5 or 6 protective factors, after adjusting for age, sex, level of education, parental history of dementia, history of stroke, systolic blood pressure, and total and high-density lipoprotein cholesterol.

Lifestyle benefits tended to be greater in younger participants

“APOE genotype significantly modified the association between protective factors and dementia,” the authors said. Compared with participants with protective modifiable risk profiles, participants with unfavorable modifiable risk profiles had greater risk for dementia in the low–APOE risk group (hazard ratio, 2.51) and intermediate–APOE risk group (HR, 1.39), but not in the high–APOE risk group.

“Protective associations of favorable risk profiles against dementia tended to be stronger in younger individuals than in older individuals and were most pronounced for younger individuals at low APOE risk,” Dr. Licher and colleagues said. In a sensitivity analysis that used a polygenic risk score for Alzheimer’s disease based on 27 variants other than APOE to determine participants’ genetic risk, the patterns were “attenuated yet largely comparable,” they wrote. Patterns also remained consistent when the researchers used an ideal cardiovascular health score to indicate modifiable health profiles.

“Our results confirm that individuals with a favorable profile have a lower risk of dementia than those with intermediate or unfavorable profiles based on modifiable risk factors,” they said. Unlike in a subgroup analysis of data from the FINGER study, however, “this study found that a favorable profile could not offset high APOE risk.”

The findings may have implications for clinical trial design and suggest that APOE4 carriers may need to be targeted earlier in the disease process to influence their risk for dementia.

“On the positive side, results from this study show that avoiding an unhealthy lifestyle could potentially prevent or postpone the onset of dementia in most individuals in the population (73%), namely those at low and intermediate genetic risk,” the investigators wrote. “Among these, the majority were categorized has having a favorable profile (66%), yet room for improvement is still substantial.”

The study lacked data on hearing impairment and did not capture shifts to more adverse or optimal lifestyles during follow-up. In addition, the results are based on relatively small samples in each risk category, and the estimates had wide confidence intervals. The population was older and mostly of European descent, which limits the generalizability of the findings, the authors noted.

Lifestyle factors may benefit only people with low genetic risk

“The authors’ key finding was that modifiable lifestyle risk factors were able to reduce dementia risk only in people who did not have an APOE4 allele and hence were at lower genetic risk,” said Kenneth Rockwood, MD, professor of geriatric medicine and neurology at Dalhousie University in Halifax, N.S., and his coauthors, in an accompanying editorial.

The findings contrast with those of another recent population-based study using data from the UK Biobank (JAMA. 2019;322[5]:430-7. doi: 10.1001/jama.2019.9879), which suggested that modifiable factors affect dementia risk regardless of genetic risk.

Together, these studies “tell us that ... we must better understand outcomes in those most at risk,” they said. “We might begin by recognizing that aging is essential, rather than incidental, to dementia disease expression.” Future research should focus on people living with frailty, who often are excluded from trials and are at high risk for dementia. Older adults who develop delirium also may be an ideal target group of patients at increased risk for dementia.

“Reducing the extent of disease expression in people prone to developing dementia late in life is difficult. Studies investigating whether dementia can be prevented at all, such as the Rotterdam study, and then whether it can be prevented in the people at greatest risk, can be commended for their clear-eyed approach,” Dr. Rockwood and colleagues said.

The Rotterdam Study is funded by Erasmus Medical Center and University, as well as a variety of Dutch organizations, institutes, and government ministries, and the European Commission. The authors had no competing interests.

Dr. Rockwood is president and chief science officer of DGI Clinical, which has contracts with pharmaceutical and device manufacturers related to individualized outcome measurement.

[email protected]

SOURCES: Licher S et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0547-7; and Rockwood K et al. Nat Med. 2019 Aug 26. doi: 10.1038/s41591-019-0575-3.

The gender wage gap in physician compensation persists but is narrowing. According to information gleaned from self-reported compensation surveys, collected by Doximity and completed by 90,000 full-time, US-licensed physicians, while wages for men idled between 2017 and 2018, they increased for women by 2%.¹ So, whereas the gender wage gap was 27.7% in 2017, it dropped to 25.2% in 2018. This translates to female physicians making $90,490 less than male counterparts in 2018 vs $105,000 less in 2017.¹

Gender wage gap and geography. Metropolitan areas with the smallest gender wage gaps according to the Doximity report include Birmingham, Alabama (9%); Bridgeport, Connecticut (10%); and Seattle, Washington (15%). Areas with the largest gender wage gap include Louisville/Jefferson County, Kentucky-Indiana (40%); New Orleans, Louisiana (32%); and Austin, Texas (31%).¹

Gender wage gap and specialty. Specialties with the widest gender wage gaps are pediatric pulmonology (23%), otolaryngology (22%), and urology (22%). Those with the narrowest gaps are hematology (4%), rheumatology (8%), and radiation oncology (9%).¹

Interestingly, although female physicians continue to earn less than men across the board, women were the slight majority of US medical school applicants (50.9%) and matriculants (51.6%) in 2018.²

What are physicians earning?

The overall average salary for physicians in 2019 is $313,000, according to a Medscape report, and the average annual compensation for ObGyns is $303,000, up from $300,000 in 2018.³ Doximity’s figure was slightly different; it reported average annual compensation for ObGyns to be $335,000 in 2018, ranking ObGyns 20th in specialties with the highest annual compensation.¹

Compensation by specialty. The specialties with the highest average annual compensation in 2018 according to the Doximity report were neurosurgery ($617K), thoracic surgery ($584K), and orthopedic surgery ($526K). Those with the lowest were pediatric infectious disease ($186K), pediatric endocrinology ($201K), and general pediatrics ($223K).¹

While women make up 61% of the ObGyn workforce, fewer than 15% of cardiologists, urologists, and orthopedists—some of the highest paying specialties—are women, although this alone does not explain the gender wage gap.³

Compensation by employment type. While average annual compensation increased from 2017 to 2018 for physicians working in single specialty groups (1%), multispecialty groups (1%), solo practices (3%), and industry/pharmaceutical (17%), compensation decreased for those working in health maintenance organizations (-1%), hospitals (-7%), and academia (-9%).¹ Only 14% of private practices are owned by female physicians (TABLE 1).¹

Satisfaction with compensation. Exactly half (50%) of ObGyns report feeling fairly compensated.³ Those physicians working in public health and preventive medicine are the most likely to feel fairly compensated (73%), while those working in infectious disease are least likely (42%).³
 

Location matters and may surprise you

Contrary to what many believe, less populated metropolitan areas tend to pay better than larger, more populated cities.¹ This may be because metropolitan areas without academic institutions or nationally renowned health systems tend to offer slightly higher compensation than those with such facilities. The reason? The presence of large or prestigious medical schools ensures a pipeline of viable physician candidates for limited jobs, resulting in institutions and practices needing to pay less for qualified applicants.¹

The 5 markets paying the highest physician salaries in 2018 were (from highest to lowest) Milwaukee; New Orleans; Riverside, California; Minneapolis; and Charlotte, North Carolina. Those paying the lowest were Durham, North Carolina; Providence, Rhode Island; San Antonio; Virginia Beach; and New Haven, Connecticut.¹ Rural areas continue to have problems luring physicians (see “Cures for the famine of rural physicians?”^3,4).

Job satisfaction

ObGyns rank 16th in terms of specialists who are happiest at work; 27% responded that they were very or extremely happy. Plastic surgeons ranked first in happiness on the job (41%), while those in physical medicine and rehabilitation ranked last (19%).⁵

Physicians as a whole report that the most rewarding part of the job is the gratitude from and relationships with patients, followed by “being good at a what I do”/finding answers/diagnoses, and “knowing that I’m making the world a better place.”³ Three-quarters (74%) of ObGyns would choose medicine again, and 75% would choose the same specialty. Those most likely to choose medicine again are those in infectious disease (84%), while those least likely work in physical medicine and rehabilitation (62%). Those most satisfied with their chosen specialty are ophthalmologists; 96% would choose the specialty again, whereas only 62% of internists would do so.³

Burnout. In a Medscape survey of 15,000 physicians in 29 specialties, 45% of ObGyns reported being burned out.⁵ Another 15% reported being “colloquially” depressed (sad, despondent, but not clinically depressed), and 7% reported clinical depression. While physicians overall most frequently engage in exercise as a coping mechanism, ObGyns most frequently report isolating themselves from others (47%)(TABLE 2).⁶

Across all specialties, more female physicians report being burned out than men (50% vs 39%). The 3 highest contributors to burnout are too many bureaucratic tasks (charting, paperwork), spending too many hours at work/insufficient compensation, and the increasing computerization of practices (electronic health records [EHRs])(TABLE 3).⁶ While 44% of ObGyns report that their feelings of being burned out or depressed do not affect their interactions with patients, 39% say such feelings make them easily exasperated with their patients.⁶ One in five (20%) responding ObGyns reported having had thoughts of suicide (vs 14% for physicians as a whole).^5,6

Sources of frustration on the job

Long hours. Physicians responding to the Medscape survey say that the most frustrating part of their job is having so many rules and regulations, followed by having to work with an EHR, and having to work long hours.³

As for the latter, 60% of responding ObGyns reported working long hours, which places obstetrics/gynecology in the 11th position on a list of specialties with physicians reporting working too many hours.⁵ Surgeons were number 1 with 77% reporting working long hours, and emergency medicine physicians were last with only 13% reporting working long hours.

Paper and administrative tasks. Thirty-eight percent of the physicians responding to the Medscape survey report spending 10 to 19 hours per week on paperwork; another 36% report spending 20 hours or more.³ This is almost identical to last year when the figures were 38% and 32%, respectively. However, the trend in the last few years has been dramatic. In 2017, the total percentage of physicians spending 10 of more hours on paperwork per week was 57%, compared with this year’s 74%.³
 

The gender wage gap in physician compensation persists but is narrowing. According to information gleaned from self-reported compensation surveys, collected by Doximity and completed by 90,000 full-time, US-licensed physicians, while wages for men idled between 2017 and 2018, they increased for women by 2%.¹ So, whereas the gender wage gap was 27.7% in 2017, it dropped to 25.2% in 2018. This translates to female physicians making $90,490 less than male counterparts in 2018 vs $105,000 less in 2017.¹

Gender wage gap and geography. Metropolitan areas with the smallest gender wage gaps according to the Doximity report include Birmingham, Alabama (9%); Bridgeport, Connecticut (10%); and Seattle, Washington (15%). Areas with the largest gender wage gap include Louisville/Jefferson County, Kentucky-Indiana (40%); New Orleans, Louisiana (32%); and Austin, Texas (31%).¹

Gender wage gap and specialty. Specialties with the widest gender wage gaps are pediatric pulmonology (23%), otolaryngology (22%), and urology (22%). Those with the narrowest gaps are hematology (4%), rheumatology (8%), and radiation oncology (9%).¹

Interestingly, although female physicians continue to earn less than men across the board, women were the slight majority of US medical school applicants (50.9%) and matriculants (51.6%) in 2018.²

What are physicians earning?

The overall average salary for physicians in 2019 is $313,000, according to a Medscape report, and the average annual compensation for ObGyns is $303,000, up from $300,000 in 2018.³ Doximity’s figure was slightly different; it reported average annual compensation for ObGyns to be $335,000 in 2018, ranking ObGyns 20th in specialties with the highest annual compensation.¹

Compensation by specialty. The specialties with the highest average annual compensation in 2018 according to the Doximity report were neurosurgery ($617K), thoracic surgery ($584K), and orthopedic surgery ($526K). Those with the lowest were pediatric infectious disease ($186K), pediatric endocrinology ($201K), and general pediatrics ($223K).¹

While women make up 61% of the ObGyn workforce, fewer than 15% of cardiologists, urologists, and orthopedists—some of the highest paying specialties—are women, although this alone does not explain the gender wage gap.³

Compensation by employment type. While average annual compensation increased from 2017 to 2018 for physicians working in single specialty groups (1%), multispecialty groups (1%), solo practices (3%), and industry/pharmaceutical (17%), compensation decreased for those working in health maintenance organizations (-1%), hospitals (-7%), and academia (-9%).¹ Only 14% of private practices are owned by female physicians (TABLE 1).¹

Satisfaction with compensation. Exactly half (50%) of ObGyns report feeling fairly compensated.³ Those physicians working in public health and preventive medicine are the most likely to feel fairly compensated (73%), while those working in infectious disease are least likely (42%).³
 

Location matters and may surprise you

Contrary to what many believe, less populated metropolitan areas tend to pay better than larger, more populated cities.¹ This may be because metropolitan areas without academic institutions or nationally renowned health systems tend to offer slightly higher compensation than those with such facilities. The reason? The presence of large or prestigious medical schools ensures a pipeline of viable physician candidates for limited jobs, resulting in institutions and practices needing to pay less for qualified applicants.¹

The 5 markets paying the highest physician salaries in 2018 were (from highest to lowest) Milwaukee; New Orleans; Riverside, California; Minneapolis; and Charlotte, North Carolina. Those paying the lowest were Durham, North Carolina; Providence, Rhode Island; San Antonio; Virginia Beach; and New Haven, Connecticut.¹ Rural areas continue to have problems luring physicians (see “Cures for the famine of rural physicians?”^3,4).

Job satisfaction

ObGyns rank 16th in terms of specialists who are happiest at work; 27% responded that they were very or extremely happy. Plastic surgeons ranked first in happiness on the job (41%), while those in physical medicine and rehabilitation ranked last (19%).⁵

Physicians as a whole report that the most rewarding part of the job is the gratitude from and relationships with patients, followed by “being good at a what I do”/finding answers/diagnoses, and “knowing that I’m making the world a better place.”³ Three-quarters (74%) of ObGyns would choose medicine again, and 75% would choose the same specialty. Those most likely to choose medicine again are those in infectious disease (84%), while those least likely work in physical medicine and rehabilitation (62%). Those most satisfied with their chosen specialty are ophthalmologists; 96% would choose the specialty again, whereas only 62% of internists would do so.³

Burnout. In a Medscape survey of 15,000 physicians in 29 specialties, 45% of ObGyns reported being burned out.⁵ Another 15% reported being “colloquially” depressed (sad, despondent, but not clinically depressed), and 7% reported clinical depression. While physicians overall most frequently engage in exercise as a coping mechanism, ObGyns most frequently report isolating themselves from others (47%)(TABLE 2).⁶

Across all specialties, more female physicians report being burned out than men (50% vs 39%). The 3 highest contributors to burnout are too many bureaucratic tasks (charting, paperwork), spending too many hours at work/insufficient compensation, and the increasing computerization of practices (electronic health records [EHRs])(TABLE 3).⁶ While 44% of ObGyns report that their feelings of being burned out or depressed do not affect their interactions with patients, 39% say such feelings make them easily exasperated with their patients.⁶ One in five (20%) responding ObGyns reported having had thoughts of suicide (vs 14% for physicians as a whole).^5,6

Sources of frustration on the job

Long hours. Physicians responding to the Medscape survey say that the most frustrating part of their job is having so many rules and regulations, followed by having to work with an EHR, and having to work long hours.³

As for the latter, 60% of responding ObGyns reported working long hours, which places obstetrics/gynecology in the 11th position on a list of specialties with physicians reporting working too many hours.⁵ Surgeons were number 1 with 77% reporting working long hours, and emergency medicine physicians were last with only 13% reporting working long hours.

Paper and administrative tasks. Thirty-eight percent of the physicians responding to the Medscape survey report spending 10 to 19 hours per week on paperwork; another 36% report spending 20 hours or more.³ This is almost identical to last year when the figures were 38% and 32%, respectively. However, the trend in the last few years has been dramatic. In 2017, the total percentage of physicians spending 10 of more hours on paperwork per week was 57%, compared with this year’s 74%.³
 

The gender wage gap in physician compensation persists but is narrowing. According to information gleaned from self-reported compensation surveys, collected by Doximity and completed by 90,000 full-time, US-licensed physicians, while wages for men idled between 2017 and 2018, they increased for women by 2%.¹ So, whereas the gender wage gap was 27.7% in 2017, it dropped to 25.2% in 2018. This translates to female physicians making $90,490 less than male counterparts in 2018 vs $105,000 less in 2017.¹

Gender wage gap and geography. Metropolitan areas with the smallest gender wage gaps according to the Doximity report include Birmingham, Alabama (9%); Bridgeport, Connecticut (10%); and Seattle, Washington (15%). Areas with the largest gender wage gap include Louisville/Jefferson County, Kentucky-Indiana (40%); New Orleans, Louisiana (32%); and Austin, Texas (31%).¹

Gender wage gap and specialty. Specialties with the widest gender wage gaps are pediatric pulmonology (23%), otolaryngology (22%), and urology (22%). Those with the narrowest gaps are hematology (4%), rheumatology (8%), and radiation oncology (9%).¹

Interestingly, although female physicians continue to earn less than men across the board, women were the slight majority of US medical school applicants (50.9%) and matriculants (51.6%) in 2018.²

What are physicians earning?

The overall average salary for physicians in 2019 is $313,000, according to a Medscape report, and the average annual compensation for ObGyns is $303,000, up from $300,000 in 2018.³ Doximity’s figure was slightly different; it reported average annual compensation for ObGyns to be $335,000 in 2018, ranking ObGyns 20th in specialties with the highest annual compensation.¹

Compensation by specialty. The specialties with the highest average annual compensation in 2018 according to the Doximity report were neurosurgery ($617K), thoracic surgery ($584K), and orthopedic surgery ($526K). Those with the lowest were pediatric infectious disease ($186K), pediatric endocrinology ($201K), and general pediatrics ($223K).¹

While women make up 61% of the ObGyn workforce, fewer than 15% of cardiologists, urologists, and orthopedists—some of the highest paying specialties—are women, although this alone does not explain the gender wage gap.³

Compensation by employment type. While average annual compensation increased from 2017 to 2018 for physicians working in single specialty groups (1%), multispecialty groups (1%), solo practices (3%), and industry/pharmaceutical (17%), compensation decreased for those working in health maintenance organizations (-1%), hospitals (-7%), and academia (-9%).¹ Only 14% of private practices are owned by female physicians (TABLE 1).¹

Satisfaction with compensation. Exactly half (50%) of ObGyns report feeling fairly compensated.³ Those physicians working in public health and preventive medicine are the most likely to feel fairly compensated (73%), while those working in infectious disease are least likely (42%).³
 

Location matters and may surprise you

Contrary to what many believe, less populated metropolitan areas tend to pay better than larger, more populated cities.¹ This may be because metropolitan areas without academic institutions or nationally renowned health systems tend to offer slightly higher compensation than those with such facilities. The reason? The presence of large or prestigious medical schools ensures a pipeline of viable physician candidates for limited jobs, resulting in institutions and practices needing to pay less for qualified applicants.¹

The 5 markets paying the highest physician salaries in 2018 were (from highest to lowest) Milwaukee; New Orleans; Riverside, California; Minneapolis; and Charlotte, North Carolina. Those paying the lowest were Durham, North Carolina; Providence, Rhode Island; San Antonio; Virginia Beach; and New Haven, Connecticut.¹ Rural areas continue to have problems luring physicians (see “Cures for the famine of rural physicians?”^3,4).

Job satisfaction

ObGyns rank 16th in terms of specialists who are happiest at work; 27% responded that they were very or extremely happy. Plastic surgeons ranked first in happiness on the job (41%), while those in physical medicine and rehabilitation ranked last (19%).⁵

Physicians as a whole report that the most rewarding part of the job is the gratitude from and relationships with patients, followed by “being good at a what I do”/finding answers/diagnoses, and “knowing that I’m making the world a better place.”³ Three-quarters (74%) of ObGyns would choose medicine again, and 75% would choose the same specialty. Those most likely to choose medicine again are those in infectious disease (84%), while those least likely work in physical medicine and rehabilitation (62%). Those most satisfied with their chosen specialty are ophthalmologists; 96% would choose the specialty again, whereas only 62% of internists would do so.³

Burnout. In a Medscape survey of 15,000 physicians in 29 specialties, 45% of ObGyns reported being burned out.⁵ Another 15% reported being “colloquially” depressed (sad, despondent, but not clinically depressed), and 7% reported clinical depression. While physicians overall most frequently engage in exercise as a coping mechanism, ObGyns most frequently report isolating themselves from others (47%)(TABLE 2).⁶

Across all specialties, more female physicians report being burned out than men (50% vs 39%). The 3 highest contributors to burnout are too many bureaucratic tasks (charting, paperwork), spending too many hours at work/insufficient compensation, and the increasing computerization of practices (electronic health records [EHRs])(TABLE 3).⁶ While 44% of ObGyns report that their feelings of being burned out or depressed do not affect their interactions with patients, 39% say such feelings make them easily exasperated with their patients.⁶ One in five (20%) responding ObGyns reported having had thoughts of suicide (vs 14% for physicians as a whole).^5,6

Sources of frustration on the job

Long hours. Physicians responding to the Medscape survey say that the most frustrating part of their job is having so many rules and regulations, followed by having to work with an EHR, and having to work long hours.³

As for the latter, 60% of responding ObGyns reported working long hours, which places obstetrics/gynecology in the 11th position on a list of specialties with physicians reporting working too many hours.⁵ Surgeons were number 1 with 77% reporting working long hours, and emergency medicine physicians were last with only 13% reporting working long hours.

Paper and administrative tasks. Thirty-eight percent of the physicians responding to the Medscape survey report spending 10 to 19 hours per week on paperwork; another 36% report spending 20 hours or more.³ This is almost identical to last year when the figures were 38% and 32%, respectively. However, the trend in the last few years has been dramatic. In 2017, the total percentage of physicians spending 10 of more hours on paperwork per week was 57%, compared with this year’s 74%.³
 

ORANGE, CALIF. – When Shannon Suo, MD, reached her family medicine rotation as a medical student at the University of Cincinnati, she recalls that the faculty “seemed a little lost” when they encountered patients who presented with psychiatric issues.

“If it were diabetes, high blood pressure, or back pain, they knew what to do; they had a plan,” said Dr. Suo, who is now training director for the combined family medicine/psychiatry residency at the University of California, Davis. “But when it came to depression, anxiety, maybe even some psychosis, they kind of looked a little nervous. Maybe they prescribed an antidepressant, but then they were like, ‘I don’t know what else to do for you.’ I felt uncomfortable with that.”

Eric Eschweiler, DNP, can identify with that sentiment. After he assumed the medical directorship of a federally qualified health center that opened 4 years ago in San Bernardino, Calif., nearly every person who presented for treatment had an underlying psychiatric disorder, from depression and anxiety to bipolar disorder and substance abuse stemming from childhood trauma.

“I really felt unprepared to take care of that population because with those mental health disorders, we would get a lot of concomitant chronic medical conditions,” Dr. Eschweiler said. “But they were not adherent, not compliant because they couldn’t control the mental health aspects, or we couldn’t get a handle on those issues.

“In [nurse practitioner] training, we really don’t get a whole lot of education related to the psychiatric component of health care,” he said. “I have a doctorate, but even with that, we didn’t get very much.”

When Dr. Eschweiler learned about a yearlong clinical fellowship designed for primary care–oriented trainees and clinicians who wish to receive advanced training in primary care psychiatry, he applied, “hoping I’d be first in line,” he said. He earned a spot in the 2018 class.

The program, known as the UC Irvine/UC Davis Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship, launched in 2016 as a way to train primary care clinicians to diagnose and treat the most common psychiatric conditions found in the primary care setting. The fellowship is aimed at educating not only MDs and DOs, but physician assistants, nurse practitioners, and pharmacists as well.

Doug Brunk/MDedge News

“We want to give high-quality training to as many people as we can in order to optimize and expand the psychiatric workforce,” said Robert M. McCarron, DO, founding codirector of the fellowship program, and professor and vice chair of education and integrated care at the University of California, Irvine. “That’s really what we’re trying to do here.”

According to Dr. McCarron, who founded the fellowship with seed money during his tenure as a faculty member at UC Davis, up to 60% of all behavioral health care is provided in the busy primary setting, and as many as 80% of antidepressants are prescribed by nonpsychiatrists. Couple that with the current psychiatric workforce shortage “and you have a perfect storm,” he said.

“The toughest part is the volume of patients primary care providers have to see, comingled with a high frequency of comorbid mental illness. Added on to that, they didn’t get the training for much of the conditions they’re trying to address or treat. A primary care provider can refer to a psychiatrist, but there is not a large referral base. In addition, plenty of studies show that about half of those patients don’t end up seeing a mental health provider. Resources are limited in many areas of the country.”

TNT PCP fellows participate in the year-long program during nonclinic hours and accrue more than 45 CME units. Much of the training involves online courses framed around the textbook Primary Care Psychiatry (Wolters Kluwer, 2019), but fellows also are required to attend two intensive weekend sessions where they drill down on core topics, such as how to conduct an effective psychiatric interview, techniques, and how to screen and treat for psychiatric disorders.

“It’s not just about medicine options,” said Jaesu Han, MD, a fellowship faculty member who is board certified in psychiatry and family medicine. “For example, we try to focus on basic principles of cognitive-behavioral therapy, the role of psychotherapy, and the role of motivational interviewing. We try to help the providers recognize that there are other tools available [besides medication]. Those principles are going to help them engage with their patients more and have a larger impact.”

During one of the intensive weekend sessions, fellows are required to give a PowerPoint lecture on a topic of their choosing, with the idea of getting them comfortable with training their primary care colleagues on principles they learn.

“Some fellows are training their staff on their lunch breaks, or they’re implementing different tools they learned in our program to their organization,” said Wendy Cant, MBA, who is TNT PCP’s administrative director.

During a PowerPoint presentation a few years ago, one fellow chose to lecture about how to administer long-term antipsychotic medication in the primary care setting, a topic that the TNT PCP faculty had not thought to recommend. “We thought that was something a primary care provider would punt on,” said Dr. Suo, who is codirector of the fellowship program. “The fellow said, ‘No. This makes absolute sense. Our offices are equipped to do IM injections; our medical staff are trained to do that. It’s something that improves adherence and outcomes. It stabilizes people, and it makes us better able to take care of that population and not have to punt.’ That was unexpected and gratifying to know that we increased his comfort level to that point.”

Fellows also participate in two interactive learning sessions per month with faculty members, and each is paired with a faculty mentor, with whom they meet monthly in person or by video call or phone call.

“One of my fellows is feeling overwhelmed because she’s been tasked with taking care of the general psychiatric population, to do initial triage before she refers off to one of very few psychiatrists,” said Matthew Reed, MD, MSPH, one of the faculty mentors who serves as director of education for TNT PCP. “Her biggest concern is, ‘How do I not hate what I’m doing with my job because it’s so stressful and all patients want are opioid analgesics, or all they want are some benzodiazepines? They always want something, and I can’t get them to do what I want them to do.’ ” Together, they discuss various tools that might help her situation, such as using motivational interviewing to foster a sense of collaboration with patients.

Dr. Reed used the analogy of skeet shooting to illustrate the point that, without inviting patients to share in decision making, they are more likely to “shoot down” interventions that clinicians suggest to them.

Currently, about 80% of the program’s 118 fellows practice in California, there is a similar proportion of men and women, and their experience levels range from trainees to seasoned clinicians.

“They have 10, 15, and in some cases 25 years of experience, and they’re saying, ‘I‘ve been practicing for years and have been struggling when it comes to psychiatric issues. I want to do better,’ ” Dr. Suo noted.

Tuition is $15,500, and it usually is covered by outside funding sources. Last year, the program received a $1 million grant from California’s Office of Statewide Health Planning and Development, which was enough to fund tuition for 62 fellows. TNT PCP administrators and faculty also formed sponsor partnerships with several health plans and counties, including Inland Empire Health Plan, LA Care, Alameda Health Consortium, and Fresno County.

Employers also have stepped up. Cedars-Sinai Medical Center recently supplied a grant to fund tuition for 30 affiliated clinicians from different service planning areas. Other organizations that support funding for the fellowship include the American Academy of Pediatrics, the California Academy of Family Physicians, the California Behavioral Health Directors Association, and the California Psychiatric Association.

Meanwhile, word about the TNT PCP program is spreading to clinicians in other states. “By far, the hardest part is helping fellows from out of state find funding in their area,” Ms. Cant said. “That’s new territory we are starting to look into, but typically it’s not out of pocket. We only had three people pay out of pocket last year.”

Program faculty hope to not only improve the fellows’ knowledge in psychiatry and better treatment for depression, anxiety, and substance abuse, but also decrease prescription of opioids and decrease the stigma that some clinicians might perceive in mental illness. “People come to our fellowship feeling like there’s a void in their training,” Dr. Suo said. “We’re able to fill that void. In the first year, we had a fellow who said that, after completing the program, she felt physically less tired at the end of the day, because she had been so anxious about what to do for her patients who came in with mental health complaints.

“Now she knows what to do, so she can relax and listen to them – and be more connected.”

In the spirit of paying his TNT PCP education forward, last year Dr. Eschweiler secured a Song Brown grant to implement a 2-day psychiatric course for family medicine NP students at Western University of Health Sciences in Pomona, Calif., where he holds a faculty post. After they completed the course, students spent 80 hours with Dr. Eschweiler or with a designated clinician in the clinic, where they applied what they learned.

“By the time we shared information with students who I received in the TNT PCP fellowship, their comfort level went up by 80%-90%,” he said. “Now, they’re able to move into practice and take care of a lot of these patients without having to punt.”

Such stories are heartening to TNT PCP faculty. “We simply do not have enough psychiatrists in the country to provide mental health care for everybody who needs it,” Dr. Suo said. “Unfortunately, that means primary care will have to take up the slack. We want to prepare people to be able to do that.”

For information about the 2020 TNT PCP Fellowship, visit www.psychiatry.uci.edu/tnt.

[email protected]

ORANGE, CALIF. – When Shannon Suo, MD, reached her family medicine rotation as a medical student at the University of Cincinnati, she recalls that the faculty “seemed a little lost” when they encountered patients who presented with psychiatric issues.

“If it were diabetes, high blood pressure, or back pain, they knew what to do; they had a plan,” said Dr. Suo, who is now training director for the combined family medicine/psychiatry residency at the University of California, Davis. “But when it came to depression, anxiety, maybe even some psychosis, they kind of looked a little nervous. Maybe they prescribed an antidepressant, but then they were like, ‘I don’t know what else to do for you.’ I felt uncomfortable with that.”

Eric Eschweiler, DNP, can identify with that sentiment. After he assumed the medical directorship of a federally qualified health center that opened 4 years ago in San Bernardino, Calif., nearly every person who presented for treatment had an underlying psychiatric disorder, from depression and anxiety to bipolar disorder and substance abuse stemming from childhood trauma.

“I really felt unprepared to take care of that population because with those mental health disorders, we would get a lot of concomitant chronic medical conditions,” Dr. Eschweiler said. “But they were not adherent, not compliant because they couldn’t control the mental health aspects, or we couldn’t get a handle on those issues.

“In [nurse practitioner] training, we really don’t get a whole lot of education related to the psychiatric component of health care,” he said. “I have a doctorate, but even with that, we didn’t get very much.”

When Dr. Eschweiler learned about a yearlong clinical fellowship designed for primary care–oriented trainees and clinicians who wish to receive advanced training in primary care psychiatry, he applied, “hoping I’d be first in line,” he said. He earned a spot in the 2018 class.

The program, known as the UC Irvine/UC Davis Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship, launched in 2016 as a way to train primary care clinicians to diagnose and treat the most common psychiatric conditions found in the primary care setting. The fellowship is aimed at educating not only MDs and DOs, but physician assistants, nurse practitioners, and pharmacists as well.

Doug Brunk/MDedge News

“We want to give high-quality training to as many people as we can in order to optimize and expand the psychiatric workforce,” said Robert M. McCarron, DO, founding codirector of the fellowship program, and professor and vice chair of education and integrated care at the University of California, Irvine. “That’s really what we’re trying to do here.”

According to Dr. McCarron, who founded the fellowship with seed money during his tenure as a faculty member at UC Davis, up to 60% of all behavioral health care is provided in the busy primary setting, and as many as 80% of antidepressants are prescribed by nonpsychiatrists. Couple that with the current psychiatric workforce shortage “and you have a perfect storm,” he said.

“The toughest part is the volume of patients primary care providers have to see, comingled with a high frequency of comorbid mental illness. Added on to that, they didn’t get the training for much of the conditions they’re trying to address or treat. A primary care provider can refer to a psychiatrist, but there is not a large referral base. In addition, plenty of studies show that about half of those patients don’t end up seeing a mental health provider. Resources are limited in many areas of the country.”

TNT PCP fellows participate in the year-long program during nonclinic hours and accrue more than 45 CME units. Much of the training involves online courses framed around the textbook Primary Care Psychiatry (Wolters Kluwer, 2019), but fellows also are required to attend two intensive weekend sessions where they drill down on core topics, such as how to conduct an effective psychiatric interview, techniques, and how to screen and treat for psychiatric disorders.

“It’s not just about medicine options,” said Jaesu Han, MD, a fellowship faculty member who is board certified in psychiatry and family medicine. “For example, we try to focus on basic principles of cognitive-behavioral therapy, the role of psychotherapy, and the role of motivational interviewing. We try to help the providers recognize that there are other tools available [besides medication]. Those principles are going to help them engage with their patients more and have a larger impact.”

During one of the intensive weekend sessions, fellows are required to give a PowerPoint lecture on a topic of their choosing, with the idea of getting them comfortable with training their primary care colleagues on principles they learn.

“Some fellows are training their staff on their lunch breaks, or they’re implementing different tools they learned in our program to their organization,” said Wendy Cant, MBA, who is TNT PCP’s administrative director.

During a PowerPoint presentation a few years ago, one fellow chose to lecture about how to administer long-term antipsychotic medication in the primary care setting, a topic that the TNT PCP faculty had not thought to recommend. “We thought that was something a primary care provider would punt on,” said Dr. Suo, who is codirector of the fellowship program. “The fellow said, ‘No. This makes absolute sense. Our offices are equipped to do IM injections; our medical staff are trained to do that. It’s something that improves adherence and outcomes. It stabilizes people, and it makes us better able to take care of that population and not have to punt.’ That was unexpected and gratifying to know that we increased his comfort level to that point.”

Fellows also participate in two interactive learning sessions per month with faculty members, and each is paired with a faculty mentor, with whom they meet monthly in person or by video call or phone call.

“One of my fellows is feeling overwhelmed because she’s been tasked with taking care of the general psychiatric population, to do initial triage before she refers off to one of very few psychiatrists,” said Matthew Reed, MD, MSPH, one of the faculty mentors who serves as director of education for TNT PCP. “Her biggest concern is, ‘How do I not hate what I’m doing with my job because it’s so stressful and all patients want are opioid analgesics, or all they want are some benzodiazepines? They always want something, and I can’t get them to do what I want them to do.’ ” Together, they discuss various tools that might help her situation, such as using motivational interviewing to foster a sense of collaboration with patients.

Dr. Reed used the analogy of skeet shooting to illustrate the point that, without inviting patients to share in decision making, they are more likely to “shoot down” interventions that clinicians suggest to them.

Currently, about 80% of the program’s 118 fellows practice in California, there is a similar proportion of men and women, and their experience levels range from trainees to seasoned clinicians.

“They have 10, 15, and in some cases 25 years of experience, and they’re saying, ‘I‘ve been practicing for years and have been struggling when it comes to psychiatric issues. I want to do better,’ ” Dr. Suo noted.

Tuition is $15,500, and it usually is covered by outside funding sources. Last year, the program received a $1 million grant from California’s Office of Statewide Health Planning and Development, which was enough to fund tuition for 62 fellows. TNT PCP administrators and faculty also formed sponsor partnerships with several health plans and counties, including Inland Empire Health Plan, LA Care, Alameda Health Consortium, and Fresno County.

Employers also have stepped up. Cedars-Sinai Medical Center recently supplied a grant to fund tuition for 30 affiliated clinicians from different service planning areas. Other organizations that support funding for the fellowship include the American Academy of Pediatrics, the California Academy of Family Physicians, the California Behavioral Health Directors Association, and the California Psychiatric Association.

Meanwhile, word about the TNT PCP program is spreading to clinicians in other states. “By far, the hardest part is helping fellows from out of state find funding in their area,” Ms. Cant said. “That’s new territory we are starting to look into, but typically it’s not out of pocket. We only had three people pay out of pocket last year.”

Program faculty hope to not only improve the fellows’ knowledge in psychiatry and better treatment for depression, anxiety, and substance abuse, but also decrease prescription of opioids and decrease the stigma that some clinicians might perceive in mental illness. “People come to our fellowship feeling like there’s a void in their training,” Dr. Suo said. “We’re able to fill that void. In the first year, we had a fellow who said that, after completing the program, she felt physically less tired at the end of the day, because she had been so anxious about what to do for her patients who came in with mental health complaints.

“Now she knows what to do, so she can relax and listen to them – and be more connected.”

In the spirit of paying his TNT PCP education forward, last year Dr. Eschweiler secured a Song Brown grant to implement a 2-day psychiatric course for family medicine NP students at Western University of Health Sciences in Pomona, Calif., where he holds a faculty post. After they completed the course, students spent 80 hours with Dr. Eschweiler or with a designated clinician in the clinic, where they applied what they learned.

“By the time we shared information with students who I received in the TNT PCP fellowship, their comfort level went up by 80%-90%,” he said. “Now, they’re able to move into practice and take care of a lot of these patients without having to punt.”

Such stories are heartening to TNT PCP faculty. “We simply do not have enough psychiatrists in the country to provide mental health care for everybody who needs it,” Dr. Suo said. “Unfortunately, that means primary care will have to take up the slack. We want to prepare people to be able to do that.”

For information about the 2020 TNT PCP Fellowship, visit www.psychiatry.uci.edu/tnt.

[email protected]

ORANGE, CALIF. – When Shannon Suo, MD, reached her family medicine rotation as a medical student at the University of Cincinnati, she recalls that the faculty “seemed a little lost” when they encountered patients who presented with psychiatric issues.

“If it were diabetes, high blood pressure, or back pain, they knew what to do; they had a plan,” said Dr. Suo, who is now training director for the combined family medicine/psychiatry residency at the University of California, Davis. “But when it came to depression, anxiety, maybe even some psychosis, they kind of looked a little nervous. Maybe they prescribed an antidepressant, but then they were like, ‘I don’t know what else to do for you.’ I felt uncomfortable with that.”

Eric Eschweiler, DNP, can identify with that sentiment. After he assumed the medical directorship of a federally qualified health center that opened 4 years ago in San Bernardino, Calif., nearly every person who presented for treatment had an underlying psychiatric disorder, from depression and anxiety to bipolar disorder and substance abuse stemming from childhood trauma.

“I really felt unprepared to take care of that population because with those mental health disorders, we would get a lot of concomitant chronic medical conditions,” Dr. Eschweiler said. “But they were not adherent, not compliant because they couldn’t control the mental health aspects, or we couldn’t get a handle on those issues.

“In [nurse practitioner] training, we really don’t get a whole lot of education related to the psychiatric component of health care,” he said. “I have a doctorate, but even with that, we didn’t get very much.”

When Dr. Eschweiler learned about a yearlong clinical fellowship designed for primary care–oriented trainees and clinicians who wish to receive advanced training in primary care psychiatry, he applied, “hoping I’d be first in line,” he said. He earned a spot in the 2018 class.

The program, known as the UC Irvine/UC Davis Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship, launched in 2016 as a way to train primary care clinicians to diagnose and treat the most common psychiatric conditions found in the primary care setting. The fellowship is aimed at educating not only MDs and DOs, but physician assistants, nurse practitioners, and pharmacists as well.

Doug Brunk/MDedge News

“We want to give high-quality training to as many people as we can in order to optimize and expand the psychiatric workforce,” said Robert M. McCarron, DO, founding codirector of the fellowship program, and professor and vice chair of education and integrated care at the University of California, Irvine. “That’s really what we’re trying to do here.”

According to Dr. McCarron, who founded the fellowship with seed money during his tenure as a faculty member at UC Davis, up to 60% of all behavioral health care is provided in the busy primary setting, and as many as 80% of antidepressants are prescribed by nonpsychiatrists. Couple that with the current psychiatric workforce shortage “and you have a perfect storm,” he said.

“The toughest part is the volume of patients primary care providers have to see, comingled with a high frequency of comorbid mental illness. Added on to that, they didn’t get the training for much of the conditions they’re trying to address or treat. A primary care provider can refer to a psychiatrist, but there is not a large referral base. In addition, plenty of studies show that about half of those patients don’t end up seeing a mental health provider. Resources are limited in many areas of the country.”

TNT PCP fellows participate in the year-long program during nonclinic hours and accrue more than 45 CME units. Much of the training involves online courses framed around the textbook Primary Care Psychiatry (Wolters Kluwer, 2019), but fellows also are required to attend two intensive weekend sessions where they drill down on core topics, such as how to conduct an effective psychiatric interview, techniques, and how to screen and treat for psychiatric disorders.

“It’s not just about medicine options,” said Jaesu Han, MD, a fellowship faculty member who is board certified in psychiatry and family medicine. “For example, we try to focus on basic principles of cognitive-behavioral therapy, the role of psychotherapy, and the role of motivational interviewing. We try to help the providers recognize that there are other tools available [besides medication]. Those principles are going to help them engage with their patients more and have a larger impact.”

During one of the intensive weekend sessions, fellows are required to give a PowerPoint lecture on a topic of their choosing, with the idea of getting them comfortable with training their primary care colleagues on principles they learn.

“Some fellows are training their staff on their lunch breaks, or they’re implementing different tools they learned in our program to their organization,” said Wendy Cant, MBA, who is TNT PCP’s administrative director.

During a PowerPoint presentation a few years ago, one fellow chose to lecture about how to administer long-term antipsychotic medication in the primary care setting, a topic that the TNT PCP faculty had not thought to recommend. “We thought that was something a primary care provider would punt on,” said Dr. Suo, who is codirector of the fellowship program. “The fellow said, ‘No. This makes absolute sense. Our offices are equipped to do IM injections; our medical staff are trained to do that. It’s something that improves adherence and outcomes. It stabilizes people, and it makes us better able to take care of that population and not have to punt.’ That was unexpected and gratifying to know that we increased his comfort level to that point.”

Fellows also participate in two interactive learning sessions per month with faculty members, and each is paired with a faculty mentor, with whom they meet monthly in person or by video call or phone call.

“One of my fellows is feeling overwhelmed because she’s been tasked with taking care of the general psychiatric population, to do initial triage before she refers off to one of very few psychiatrists,” said Matthew Reed, MD, MSPH, one of the faculty mentors who serves as director of education for TNT PCP. “Her biggest concern is, ‘How do I not hate what I’m doing with my job because it’s so stressful and all patients want are opioid analgesics, or all they want are some benzodiazepines? They always want something, and I can’t get them to do what I want them to do.’ ” Together, they discuss various tools that might help her situation, such as using motivational interviewing to foster a sense of collaboration with patients.

Dr. Reed used the analogy of skeet shooting to illustrate the point that, without inviting patients to share in decision making, they are more likely to “shoot down” interventions that clinicians suggest to them.

Currently, about 80% of the program’s 118 fellows practice in California, there is a similar proportion of men and women, and their experience levels range from trainees to seasoned clinicians.

“They have 10, 15, and in some cases 25 years of experience, and they’re saying, ‘I‘ve been practicing for years and have been struggling when it comes to psychiatric issues. I want to do better,’ ” Dr. Suo noted.

Tuition is $15,500, and it usually is covered by outside funding sources. Last year, the program received a $1 million grant from California’s Office of Statewide Health Planning and Development, which was enough to fund tuition for 62 fellows. TNT PCP administrators and faculty also formed sponsor partnerships with several health plans and counties, including Inland Empire Health Plan, LA Care, Alameda Health Consortium, and Fresno County.

Employers also have stepped up. Cedars-Sinai Medical Center recently supplied a grant to fund tuition for 30 affiliated clinicians from different service planning areas. Other organizations that support funding for the fellowship include the American Academy of Pediatrics, the California Academy of Family Physicians, the California Behavioral Health Directors Association, and the California Psychiatric Association.

Meanwhile, word about the TNT PCP program is spreading to clinicians in other states. “By far, the hardest part is helping fellows from out of state find funding in their area,” Ms. Cant said. “That’s new territory we are starting to look into, but typically it’s not out of pocket. We only had three people pay out of pocket last year.”

Program faculty hope to not only improve the fellows’ knowledge in psychiatry and better treatment for depression, anxiety, and substance abuse, but also decrease prescription of opioids and decrease the stigma that some clinicians might perceive in mental illness. “People come to our fellowship feeling like there’s a void in their training,” Dr. Suo said. “We’re able to fill that void. In the first year, we had a fellow who said that, after completing the program, she felt physically less tired at the end of the day, because she had been so anxious about what to do for her patients who came in with mental health complaints.

“Now she knows what to do, so she can relax and listen to them – and be more connected.”

In the spirit of paying his TNT PCP education forward, last year Dr. Eschweiler secured a Song Brown grant to implement a 2-day psychiatric course for family medicine NP students at Western University of Health Sciences in Pomona, Calif., where he holds a faculty post. After they completed the course, students spent 80 hours with Dr. Eschweiler or with a designated clinician in the clinic, where they applied what they learned.

“By the time we shared information with students who I received in the TNT PCP fellowship, their comfort level went up by 80%-90%,” he said. “Now, they’re able to move into practice and take care of a lot of these patients without having to punt.”

Such stories are heartening to TNT PCP faculty. “We simply do not have enough psychiatrists in the country to provide mental health care for everybody who needs it,” Dr. Suo said. “Unfortunately, that means primary care will have to take up the slack. We want to prepare people to be able to do that.”

For information about the 2020 TNT PCP Fellowship, visit www.psychiatry.uci.edu/tnt.

[email protected]

[polldaddy:10359495]

[polldaddy:10359495]

[polldaddy:10359495]

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

In a sampling of 300 individuals with a mean age of 41 years and nearly 16 self-reported headache days per month over the past 6 months, respondents agreed that they were willing to trade some degree of efficacy for less severe adverse events—namely weight gain and memory problems—and that they were even willing to pay more for these tradeoffs in some cases. On average, respondents were willing to pay:

• $84 more (95% confidence interval [CI], $64‐$103) per month to avoid a 10% weight gain
• $59 more (95% CI, $42‐$76) per month to avoid memory problems
• $35 more (95% CI, $20‐$51) per month to avoid a 5% weight gain, and
• $32 (95% CI, $18‐$46) per month to avoid thinking problems.

Within the pool, 81% of respondents confirmed that they had taken a prescription medicine to prevent migraine in the past 6 months.

I think the broad message of this study is important: migraine is not just about migraine or headache days per month. This should not come as news to anyone with more than a passing interest in this condition. As an epidemiological study, it is useful to understand how migraine patients, as a group, view the relative value of cost, side effects, etc. For clinicians, the value of this study is to remind us of the complexity we need to consider when prescribing a migraine treatment. Issues of co-morbidity, economic resources, type of work or daily activities, and most bothersome symptom all play into the decision process, and it is critical to have the patient expressly involved in this process. It is not just about migraine days. It never has been.

Implicit in this article is the reality that we now have a wide variety of pharmacologic and device options for treating migraine. In the past, this was not the case. There is no clear winner among the preventives in terms of headache or migraine days per month. Rather, as the article suggests, we now have the option of selecting our preventives based on a cost-benefit analysis. Because of the near parity in terms of efficacy, the choices are often based on accessibility, financial burden, delivery system, and side effect profile. Properly presented, this can be an empowering experience for the patient. Choices may involve the need for trialing one or more treatments before gaining access to a preferred treatment, or the willingness to risk the chance of an untoward side effect against the promise of a more convivial dosing regimen. This collaborative decision-making process helps center the locus of control with the patient and secure a healthy relationship between the provider and patient.

It should also be remembered that the promise of a given side effect profile is based on the observation in trials and does not reflect the probability of a given outcome in a single patient. Neither does the side effect profile generated in a controlled trial necessarily reflect the side effect profile in any given individual. Too often we fail to stress this to patients and a 1% risk becomes an unavoidable consequence or a promise of smooth sailing. Time spent educating patients (and providers) with regard to the interpretation of efficacy and risk data, is time well spent.

Dr. Cowan is a Higgins Professor of Neurology, Chief of the Division of Headache Medicine and the Department of Neurology and Neurosciences, and Director of the Center for Headache and Facial Pain, at Stanford University School of Medicine.

In a sampling of 300 individuals with a mean age of 41 years and nearly 16 self-reported headache days per month over the past 6 months, respondents agreed that they were willing to trade some degree of efficacy for less severe adverse events—namely weight gain and memory problems—and that they were even willing to pay more for these tradeoffs in some cases. On average, respondents were willing to pay:

• $84 more (95% confidence interval [CI], $64‐$103) per month to avoid a 10% weight gain
• $59 more (95% CI, $42‐$76) per month to avoid memory problems
• $35 more (95% CI, $20‐$51) per month to avoid a 5% weight gain, and
• $32 (95% CI, $18‐$46) per month to avoid thinking problems.

Within the pool, 81% of respondents confirmed that they had taken a prescription medicine to prevent migraine in the past 6 months.

I think the broad message of this study is important: migraine is not just about migraine or headache days per month. This should not come as news to anyone with more than a passing interest in this condition. As an epidemiological study, it is useful to understand how migraine patients, as a group, view the relative value of cost, side effects, etc. For clinicians, the value of this study is to remind us of the complexity we need to consider when prescribing a migraine treatment. Issues of co-morbidity, economic resources, type of work or daily activities, and most bothersome symptom all play into the decision process, and it is critical to have the patient expressly involved in this process. It is not just about migraine days. It never has been.

Implicit in this article is the reality that we now have a wide variety of pharmacologic and device options for treating migraine. In the past, this was not the case. There is no clear winner among the preventives in terms of headache or migraine days per month. Rather, as the article suggests, we now have the option of selecting our preventives based on a cost-benefit analysis. Because of the near parity in terms of efficacy, the choices are often based on accessibility, financial burden, delivery system, and side effect profile. Properly presented, this can be an empowering experience for the patient. Choices may involve the need for trialing one or more treatments before gaining access to a preferred treatment, or the willingness to risk the chance of an untoward side effect against the promise of a more convivial dosing regimen. This collaborative decision-making process helps center the locus of control with the patient and secure a healthy relationship between the provider and patient.

It should also be remembered that the promise of a given side effect profile is based on the observation in trials and does not reflect the probability of a given outcome in a single patient. Neither does the side effect profile generated in a controlled trial necessarily reflect the side effect profile in any given individual. Too often we fail to stress this to patients and a 1% risk becomes an unavoidable consequence or a promise of smooth sailing. Time spent educating patients (and providers) with regard to the interpretation of efficacy and risk data, is time well spent.

Dr. Cowan is a Higgins Professor of Neurology, Chief of the Division of Headache Medicine and the Department of Neurology and Neurosciences, and Director of the Center for Headache and Facial Pain, at Stanford University School of Medicine.

In a sampling of 300 individuals with a mean age of 41 years and nearly 16 self-reported headache days per month over the past 6 months, respondents agreed that they were willing to trade some degree of efficacy for less severe adverse events—namely weight gain and memory problems—and that they were even willing to pay more for these tradeoffs in some cases. On average, respondents were willing to pay:

• $84 more (95% confidence interval [CI], $64‐$103) per month to avoid a 10% weight gain
• $59 more (95% CI, $42‐$76) per month to avoid memory problems
• $35 more (95% CI, $20‐$51) per month to avoid a 5% weight gain, and
• $32 (95% CI, $18‐$46) per month to avoid thinking problems.

Within the pool, 81% of respondents confirmed that they had taken a prescription medicine to prevent migraine in the past 6 months.

I think the broad message of this study is important: migraine is not just about migraine or headache days per month. This should not come as news to anyone with more than a passing interest in this condition. As an epidemiological study, it is useful to understand how migraine patients, as a group, view the relative value of cost, side effects, etc. For clinicians, the value of this study is to remind us of the complexity we need to consider when prescribing a migraine treatment. Issues of co-morbidity, economic resources, type of work or daily activities, and most bothersome symptom all play into the decision process, and it is critical to have the patient expressly involved in this process. It is not just about migraine days. It never has been.

Implicit in this article is the reality that we now have a wide variety of pharmacologic and device options for treating migraine. In the past, this was not the case. There is no clear winner among the preventives in terms of headache or migraine days per month. Rather, as the article suggests, we now have the option of selecting our preventives based on a cost-benefit analysis. Because of the near parity in terms of efficacy, the choices are often based on accessibility, financial burden, delivery system, and side effect profile. Properly presented, this can be an empowering experience for the patient. Choices may involve the need for trialing one or more treatments before gaining access to a preferred treatment, or the willingness to risk the chance of an untoward side effect against the promise of a more convivial dosing regimen. This collaborative decision-making process helps center the locus of control with the patient and secure a healthy relationship between the provider and patient.

It should also be remembered that the promise of a given side effect profile is based on the observation in trials and does not reflect the probability of a given outcome in a single patient. Neither does the side effect profile generated in a controlled trial necessarily reflect the side effect profile in any given individual. Too often we fail to stress this to patients and a 1% risk becomes an unavoidable consequence or a promise of smooth sailing. Time spent educating patients (and providers) with regard to the interpretation of efficacy and risk data, is time well spent.

Dr. Cowan is a Higgins Professor of Neurology, Chief of the Division of Headache Medicine and the Department of Neurology and Neurosciences, and Director of the Center for Headache and Facial Pain, at Stanford University School of Medicine.

Many readers may be aware of large payments made by such companies as Johnson & Johnson to compensate women with a history of ovarian cancer who have claimed that perineal application of talc played a causative role in their cancer development. This column serves to review the purported role of perineal talc use in the development of ovarian cancer, and explore some of the pitfalls of observational science.

ThitareeSarmkasat/iStock/Getty Images Plus

Talc, a hydrated magnesium silicate, is the softest mineral on earth, and has been sold as a personal hygiene product for many decades. Perineal application of talc to sanitary pads, perineal skin, undergarments, and diapers has been a common practice to decrease friction, moisture build-up, and as a deodorant. Talc is chemically similar, although not identical, to asbestos and is geologically located in close proximity to the known carcinogen. In the 1970s, there were concerns raised regarding the possible contamination of cosmetic-grade talc with asbestos, which led to the development of asbestos-free forms of the substance. Given that a strong causal relationship had been established between asbestos exposure and lung and pleural cancers, there was concern that exposure to perineal talc might increase cancer risk.

In the 1980s, an association between perineal talc exposure and ovarian cancer was observed in a case-control study.¹ Since that time, multiple other observational studies, predominately case-control studies, have observed an increased ovarian cancer risk among users of perineal talc including the findings of a meta-analysis which estimated a 24%-39% increased risk for ovarian cancer among users.² Does this establish a causal relationship? For the purposes of legal cases, these associations are adequate. However, science demands a different standard when determining cause and effect.

It is not unusual to rely on observational studies to establish a causal relationship between exposure and disease when it is unethical to randomize subjects in a clinical trial to exposure of the potential harmful agent. This was the necessary methodology behind establishing that smoking causes lung cancer. Several factors must be present when relying on observational studies to establish plausible causation including an observable biologic mechanism, dose-effect response, temporal relationship, consistent effect observed in multiple study populations, and statistical strength of response. These elements should be present in a consistent and powerful enough way to balance the pitfalls of observational studies, namely biases.

A particularly problematic bias is one of recall bias, which plagues case-control studies. Case-control studies are a popular tool to measure a relationship between an exposure and a rare disease, because they are more feasible than the prospective, observational cohort studies that require very large study populations observed over very long periods of time to capture enough events of interest (in this case, cases of ovarian cancer). In case-control studies, researchers identify a cohort of patients with the outcome of interest (ovarian cancer) and compare this population to a control group of similar demographic features. They then survey directly or indirectly (through medical records) for the exposure of interest (perineal talc use).

Recall bias occurs when subjects who have the disease are more likely to have memory of exposure than do control subjects because of the natural instincts individuals have toward attribution. This is emphasized when there is public commentary, justified or not, about the potential risks of that exposure. Given the significant publicity that these lawsuits have had with companies that produced cosmetic talc, it is plausible that ovarian cancer survivors are more likely to remember and negatively attribute their talc exposure to their cancer than are subjects without cancer. Additionally, their memory of volume and duration of exposure generally is enhanced by the same pressures. The potential for this bias is eliminated in prospective, cohort observational studies such as the Women’s Health Initiative Observational Study which, among 61,576 women, half of whom reported perineal talc exposure, did not measure a difference in the development of ovarian cancers during their 12 years of mean follow-up.³

Given these inherent biases, how do studies examining the relationship between talc exposure and ovarian cancer stand up? The biologic mechanism of talc carcinogenesis is largely theoretical. As mentioned earlier, prior to the 1970s, there was some observed contamination of talc with asbestos likely caused by the geologic proximity of these minerals. Asbestos is a known carcinogen, and therefore possibly could be harmful if a contaminant of talc. However, it is not known if this level of contamination was enough to be achieve ovarian carcinogenesis. Most theories of talc carcinogenesis are based on foreign body inflammatory reaction via talc particle ascent through the genital tract. This is proposed to induce an inflammatory release of prostaglandins and cytokines, which could cause a mutagenic effect promoting carcinogenesis. The foreign body inflammatory mechanism is further supported by the observation of a decreased incidence of ovarian cancer after hysterectomy or tubal ligation.⁴ However, inconsistently, a protective effect of NSAIDs has not been observed in ovarian cancer.⁵

A recent meta-analysis, which reviewed 27 of the largest, best-quality observational studies, identified a dose-effect response with an increased risk for ovarian cancer with greater than 3,600 lifetime applications, compared with less than 3,600 applications.² The observed association between perineal talc exposure and increased risk of ovarian cancer appears to be consistent across a number of observational studies, including both case-control studies and prospective cohort studies (although somewhat mitigated in the latter). Additionally, there appears to be consistency in the finding that the risk is present for the epithelial subtypes of serous and endometrioid, but not mucinous or clear cell cancer. However, when considering the magnitude of effect, this remains somewhat small (odds ratio, 1.31; 95% confidence interval, 1.24-1.39) when compared with other better established carcinogenic relationships such as smoking and lung cancer where the hazard ratio is 12.12 (95% CI, 6.94-21.17).^2,6

If talc does not cause ovarian cancer, why would this association be observed at all? One explanation could be that talc use is a confounder for the true causative mechanism. A theoretical example of this would be if the genital microbiome (a subject we have reviewed previously in this column) was the true culprit. If a particular microbiome profile promotes both oncogenic change in the ovary while also causing vaginal discharge and odor, it might increase the likelihood that perineal talc use is reported in the history of these cancer patients. This is purely speculative, but it always is important to consider the potential for confounding variables when utilizing observational studies to attribute cause and effect.

Therefore, there is a consistently observed association between perineal talc application and ovarian cancer, however, the relationship does not appear to be strong enough, associated with a proven carcinogenic mechanism, or free from interfering recall bias such to definitively state that perineal talc exposure causes ovarian cancer. Given these findings, it is reasonable to recommend patients avoid the use of perineal talc application until further definitive safety evidence is provided. In the meantime, it should be noted that even though talc-containing products are not commercially labeled as carcinogens, many pharmaceutical and cosmetic companies have replaced the mineral talc with corn starch in their powders.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at [email protected].

References

1. Cancer. 1982 Jul 15;50(2):372-6.

2. Epidemiology. 2018 Jan;29(1):41-9.

3. J Natl Cancer Inst. 2014 Sep 10;106(9). pii: dju208.

4. Am J Epidemiol. 1991 Aug 15;134(4):362-9.

5. Int J Cancer. 2008 Jan 1;122(1):170-6.

6. J Natl Cancer Inst. 2018 Nov 1;110(11):1201-7.

Many readers may be aware of large payments made by such companies as Johnson & Johnson to compensate women with a history of ovarian cancer who have claimed that perineal application of talc played a causative role in their cancer development. This column serves to review the purported role of perineal talc use in the development of ovarian cancer, and explore some of the pitfalls of observational science.

ThitareeSarmkasat/iStock/Getty Images Plus

Talc, a hydrated magnesium silicate, is the softest mineral on earth, and has been sold as a personal hygiene product for many decades. Perineal application of talc to sanitary pads, perineal skin, undergarments, and diapers has been a common practice to decrease friction, moisture build-up, and as a deodorant. Talc is chemically similar, although not identical, to asbestos and is geologically located in close proximity to the known carcinogen. In the 1970s, there were concerns raised regarding the possible contamination of cosmetic-grade talc with asbestos, which led to the development of asbestos-free forms of the substance. Given that a strong causal relationship had been established between asbestos exposure and lung and pleural cancers, there was concern that exposure to perineal talc might increase cancer risk.

In the 1980s, an association between perineal talc exposure and ovarian cancer was observed in a case-control study.¹ Since that time, multiple other observational studies, predominately case-control studies, have observed an increased ovarian cancer risk among users of perineal talc including the findings of a meta-analysis which estimated a 24%-39% increased risk for ovarian cancer among users.² Does this establish a causal relationship? For the purposes of legal cases, these associations are adequate. However, science demands a different standard when determining cause and effect.

It is not unusual to rely on observational studies to establish a causal relationship between exposure and disease when it is unethical to randomize subjects in a clinical trial to exposure of the potential harmful agent. This was the necessary methodology behind establishing that smoking causes lung cancer. Several factors must be present when relying on observational studies to establish plausible causation including an observable biologic mechanism, dose-effect response, temporal relationship, consistent effect observed in multiple study populations, and statistical strength of response. These elements should be present in a consistent and powerful enough way to balance the pitfalls of observational studies, namely biases.

A particularly problematic bias is one of recall bias, which plagues case-control studies. Case-control studies are a popular tool to measure a relationship between an exposure and a rare disease, because they are more feasible than the prospective, observational cohort studies that require very large study populations observed over very long periods of time to capture enough events of interest (in this case, cases of ovarian cancer). In case-control studies, researchers identify a cohort of patients with the outcome of interest (ovarian cancer) and compare this population to a control group of similar demographic features. They then survey directly or indirectly (through medical records) for the exposure of interest (perineal talc use).

Recall bias occurs when subjects who have the disease are more likely to have memory of exposure than do control subjects because of the natural instincts individuals have toward attribution. This is emphasized when there is public commentary, justified or not, about the potential risks of that exposure. Given the significant publicity that these lawsuits have had with companies that produced cosmetic talc, it is plausible that ovarian cancer survivors are more likely to remember and negatively attribute their talc exposure to their cancer than are subjects without cancer. Additionally, their memory of volume and duration of exposure generally is enhanced by the same pressures. The potential for this bias is eliminated in prospective, cohort observational studies such as the Women’s Health Initiative Observational Study which, among 61,576 women, half of whom reported perineal talc exposure, did not measure a difference in the development of ovarian cancers during their 12 years of mean follow-up.³

Given these inherent biases, how do studies examining the relationship between talc exposure and ovarian cancer stand up? The biologic mechanism of talc carcinogenesis is largely theoretical. As mentioned earlier, prior to the 1970s, there was some observed contamination of talc with asbestos likely caused by the geologic proximity of these minerals. Asbestos is a known carcinogen, and therefore possibly could be harmful if a contaminant of talc. However, it is not known if this level of contamination was enough to be achieve ovarian carcinogenesis. Most theories of talc carcinogenesis are based on foreign body inflammatory reaction via talc particle ascent through the genital tract. This is proposed to induce an inflammatory release of prostaglandins and cytokines, which could cause a mutagenic effect promoting carcinogenesis. The foreign body inflammatory mechanism is further supported by the observation of a decreased incidence of ovarian cancer after hysterectomy or tubal ligation.⁴ However, inconsistently, a protective effect of NSAIDs has not been observed in ovarian cancer.⁵

A recent meta-analysis, which reviewed 27 of the largest, best-quality observational studies, identified a dose-effect response with an increased risk for ovarian cancer with greater than 3,600 lifetime applications, compared with less than 3,600 applications.² The observed association between perineal talc exposure and increased risk of ovarian cancer appears to be consistent across a number of observational studies, including both case-control studies and prospective cohort studies (although somewhat mitigated in the latter). Additionally, there appears to be consistency in the finding that the risk is present for the epithelial subtypes of serous and endometrioid, but not mucinous or clear cell cancer. However, when considering the magnitude of effect, this remains somewhat small (odds ratio, 1.31; 95% confidence interval, 1.24-1.39) when compared with other better established carcinogenic relationships such as smoking and lung cancer where the hazard ratio is 12.12 (95% CI, 6.94-21.17).^2,6

If talc does not cause ovarian cancer, why would this association be observed at all? One explanation could be that talc use is a confounder for the true causative mechanism. A theoretical example of this would be if the genital microbiome (a subject we have reviewed previously in this column) was the true culprit. If a particular microbiome profile promotes both oncogenic change in the ovary while also causing vaginal discharge and odor, it might increase the likelihood that perineal talc use is reported in the history of these cancer patients. This is purely speculative, but it always is important to consider the potential for confounding variables when utilizing observational studies to attribute cause and effect.

Therefore, there is a consistently observed association between perineal talc application and ovarian cancer, however, the relationship does not appear to be strong enough, associated with a proven carcinogenic mechanism, or free from interfering recall bias such to definitively state that perineal talc exposure causes ovarian cancer. Given these findings, it is reasonable to recommend patients avoid the use of perineal talc application until further definitive safety evidence is provided. In the meantime, it should be noted that even though talc-containing products are not commercially labeled as carcinogens, many pharmaceutical and cosmetic companies have replaced the mineral talc with corn starch in their powders.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at [email protected].

References

1. Cancer. 1982 Jul 15;50(2):372-6.

2. Epidemiology. 2018 Jan;29(1):41-9.

3. J Natl Cancer Inst. 2014 Sep 10;106(9). pii: dju208.

4. Am J Epidemiol. 1991 Aug 15;134(4):362-9.

5. Int J Cancer. 2008 Jan 1;122(1):170-6.

6. J Natl Cancer Inst. 2018 Nov 1;110(11):1201-7.

Many readers may be aware of large payments made by such companies as Johnson & Johnson to compensate women with a history of ovarian cancer who have claimed that perineal application of talc played a causative role in their cancer development. This column serves to review the purported role of perineal talc use in the development of ovarian cancer, and explore some of the pitfalls of observational science.

ThitareeSarmkasat/iStock/Getty Images Plus

Talc, a hydrated magnesium silicate, is the softest mineral on earth, and has been sold as a personal hygiene product for many decades. Perineal application of talc to sanitary pads, perineal skin, undergarments, and diapers has been a common practice to decrease friction, moisture build-up, and as a deodorant. Talc is chemically similar, although not identical, to asbestos and is geologically located in close proximity to the known carcinogen. In the 1970s, there were concerns raised regarding the possible contamination of cosmetic-grade talc with asbestos, which led to the development of asbestos-free forms of the substance. Given that a strong causal relationship had been established between asbestos exposure and lung and pleural cancers, there was concern that exposure to perineal talc might increase cancer risk.

In the 1980s, an association between perineal talc exposure and ovarian cancer was observed in a case-control study.¹ Since that time, multiple other observational studies, predominately case-control studies, have observed an increased ovarian cancer risk among users of perineal talc including the findings of a meta-analysis which estimated a 24%-39% increased risk for ovarian cancer among users.² Does this establish a causal relationship? For the purposes of legal cases, these associations are adequate. However, science demands a different standard when determining cause and effect.

It is not unusual to rely on observational studies to establish a causal relationship between exposure and disease when it is unethical to randomize subjects in a clinical trial to exposure of the potential harmful agent. This was the necessary methodology behind establishing that smoking causes lung cancer. Several factors must be present when relying on observational studies to establish plausible causation including an observable biologic mechanism, dose-effect response, temporal relationship, consistent effect observed in multiple study populations, and statistical strength of response. These elements should be present in a consistent and powerful enough way to balance the pitfalls of observational studies, namely biases.

A particularly problematic bias is one of recall bias, which plagues case-control studies. Case-control studies are a popular tool to measure a relationship between an exposure and a rare disease, because they are more feasible than the prospective, observational cohort studies that require very large study populations observed over very long periods of time to capture enough events of interest (in this case, cases of ovarian cancer). In case-control studies, researchers identify a cohort of patients with the outcome of interest (ovarian cancer) and compare this population to a control group of similar demographic features. They then survey directly or indirectly (through medical records) for the exposure of interest (perineal talc use).

Recall bias occurs when subjects who have the disease are more likely to have memory of exposure than do control subjects because of the natural instincts individuals have toward attribution. This is emphasized when there is public commentary, justified or not, about the potential risks of that exposure. Given the significant publicity that these lawsuits have had with companies that produced cosmetic talc, it is plausible that ovarian cancer survivors are more likely to remember and negatively attribute their talc exposure to their cancer than are subjects without cancer. Additionally, their memory of volume and duration of exposure generally is enhanced by the same pressures. The potential for this bias is eliminated in prospective, cohort observational studies such as the Women’s Health Initiative Observational Study which, among 61,576 women, half of whom reported perineal talc exposure, did not measure a difference in the development of ovarian cancers during their 12 years of mean follow-up.³

Given these inherent biases, how do studies examining the relationship between talc exposure and ovarian cancer stand up? The biologic mechanism of talc carcinogenesis is largely theoretical. As mentioned earlier, prior to the 1970s, there was some observed contamination of talc with asbestos likely caused by the geologic proximity of these minerals. Asbestos is a known carcinogen, and therefore possibly could be harmful if a contaminant of talc. However, it is not known if this level of contamination was enough to be achieve ovarian carcinogenesis. Most theories of talc carcinogenesis are based on foreign body inflammatory reaction via talc particle ascent through the genital tract. This is proposed to induce an inflammatory release of prostaglandins and cytokines, which could cause a mutagenic effect promoting carcinogenesis. The foreign body inflammatory mechanism is further supported by the observation of a decreased incidence of ovarian cancer after hysterectomy or tubal ligation.⁴ However, inconsistently, a protective effect of NSAIDs has not been observed in ovarian cancer.⁵

A recent meta-analysis, which reviewed 27 of the largest, best-quality observational studies, identified a dose-effect response with an increased risk for ovarian cancer with greater than 3,600 lifetime applications, compared with less than 3,600 applications.² The observed association between perineal talc exposure and increased risk of ovarian cancer appears to be consistent across a number of observational studies, including both case-control studies and prospective cohort studies (although somewhat mitigated in the latter). Additionally, there appears to be consistency in the finding that the risk is present for the epithelial subtypes of serous and endometrioid, but not mucinous or clear cell cancer. However, when considering the magnitude of effect, this remains somewhat small (odds ratio, 1.31; 95% confidence interval, 1.24-1.39) when compared with other better established carcinogenic relationships such as smoking and lung cancer where the hazard ratio is 12.12 (95% CI, 6.94-21.17).^2,6

If talc does not cause ovarian cancer, why would this association be observed at all? One explanation could be that talc use is a confounder for the true causative mechanism. A theoretical example of this would be if the genital microbiome (a subject we have reviewed previously in this column) was the true culprit. If a particular microbiome profile promotes both oncogenic change in the ovary while also causing vaginal discharge and odor, it might increase the likelihood that perineal talc use is reported in the history of these cancer patients. This is purely speculative, but it always is important to consider the potential for confounding variables when utilizing observational studies to attribute cause and effect.

Therefore, there is a consistently observed association between perineal talc application and ovarian cancer, however, the relationship does not appear to be strong enough, associated with a proven carcinogenic mechanism, or free from interfering recall bias such to definitively state that perineal talc exposure causes ovarian cancer. Given these findings, it is reasonable to recommend patients avoid the use of perineal talc application until further definitive safety evidence is provided. In the meantime, it should be noted that even though talc-containing products are not commercially labeled as carcinogens, many pharmaceutical and cosmetic companies have replaced the mineral talc with corn starch in their powders.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at [email protected].

References

1. Cancer. 1982 Jul 15;50(2):372-6.

2. Epidemiology. 2018 Jan;29(1):41-9.

3. J Natl Cancer Inst. 2014 Sep 10;106(9). pii: dju208.

4. Am J Epidemiol. 1991 Aug 15;134(4):362-9.

5. Int J Cancer. 2008 Jan 1;122(1):170-6.

6. J Natl Cancer Inst. 2018 Nov 1;110(11):1201-7.