Clinician Reviews

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

A version of this article first appeared on WebMD.com.

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

A version of this article first appeared on WebMD.com.

As health care providers work against the clock to administer as many COVID-19 vaccine doses as soon as possible, logistics aren’t the only thing standing in their way.

Misinformation – which has hampered the nation’s coronavirus response – is now hurting vaccination efforts, too.

About one in five Americans say they won’t take a COVID-19 vaccine, according to the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Even a third of health care workers have voiced their hesitance.

The spread of COVID-19 vaccine misinformation creates “a really powerful parallel pandemic to the real pandemic,” Imran Ahmed, CEO of the Center for Countering Digital Hate, told NPR. The center has tracked the links between vaccine misinformation and vaccine hesitancy during the past year.

The “infodemic” is essentially “working in concert to really undermine our capacity to contain COVID,” Mr. Ahmed said.

To help combat vaccine misinformation and address lingering concerns that people have, corporate, nonprofit, and media leaders, including this news organization, are joining a public service campaign called VaxFacts. Led by HealthGuard, the goal of the campaign is to provide facts and tools to help consumers make informed decisions about vaccines.

Steven Brill, co-CEO of HealthGuard, said credible information that comes from trusted messengers is critical to counter vaccine hesitancy.

“There’s traditionally a lot of skepticism about vaccines. That has really ramped up in the last few years based on campaigns about the measles vaccine. ... And now you have the COVID vaccine, which by everybody’s understanding has been ‘rushed,’ ” Mr. Brill said during an interview on Coronavirus in Context, a video series hosted by John Whyte, MD, chief medical officer for WebMD.

“There may be less understanding of the nature of what rushed really means. It’s still gone through the clinical trials it needs to go through.”

HealthGuard is a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites, and guides users to sources that offer trusted information. The tool is a new service from NewsGuard, which veteran journalists Mr. Brill and co-CEO Gordon Crovitz created in 2018 to combat misinformation in the news. HealthGuard, which is free for users globally through June, is specifically aimed at informing readers about health myths related to vaccines and COVID-19. It will cost $35 per year after that.

The HealthGuard Coronavirus Tracking Center has flagged nearly 400 websites for publishing misinformation about the coronavirus, including several top myths about COVID-19 vaccines:

• The mRNA vaccines can alter human DNA.
• Vaccines will use microchip surveillance technology.
• COVID-19 vaccines cause infertility.
• The vaccine developed by Oxford University will turn people into monkeys.
• COVID-19 vaccines contain aborted human fetal tissue.

As a partner, this news organization will feature continuing coverage of COVID-19 vaccine misinformation, including articles and videos.

There will be other efforts this year. Google has launched a $3 million fund to back fact-checking organizations to counter vaccine misinformation, and social media platforms are monitoring posts that actively promote disinformation around vaccines.

The United States has distributed nearly 50 million vaccine doses, and states have administered more than 32 million of them, including 5.9 million second doses in the two-shot vaccines, according to the latest CDC update.

To reach herd immunity, about 75%-85% of Americans will need to receive a vaccine, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in December 2020.

Vaccine skepticism has increased in recent years, which has led to a decline in vaccination rates and the highest annual number of measles cases in the United States in more than 25 years, according to the Pew Research Center. In 2019, the World Health Organization named vaccine hesitancy as 1 of 10 threats to global health.

With the COVID-19 vaccines in particular, people have voiced concerns about their safety and how well they work, given their accelerated development, according to Kaiser’s poll. They’re also worried about potential side effects, the perceived role of politics in the development process, and a lack of trust in government. Others don’t trust vaccines in general or believe they may contract COVID-19 from a vaccine, the Kaiser poll found, “suggesting that messages combating particular types of misinformation may be especially important for increasing vaccine confidence.”

A version of this article first appeared on WebMD.com.

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.

Nic_Ol/Thinkstock

Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.

“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.

“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.

The study was published online Dec. 21, 2020, in Menopause.
 

Gut-brain interaction

The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.

Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.

“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.

To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).

Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).

Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.

When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).

Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.

A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).

“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.

“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”

Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.

Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
 

Link between food and mood

In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”

It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.

She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and it is important that we do not somehow imply that eating a high-fiber diet can in any way treat a major depression.”

Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.

One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”

More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.

No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

[email protected]
 

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

[email protected]
 

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

[email protected]
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.