Federal Practitioner

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

The biased discourse and double standards around antiobesity glucagon-like peptide 1 (GLP-1) receptor agonists continue apace, most recently in The New England Journal of Medicine (NEJM) where some economists opined that their coverage would be disastrous for Medicare.

Among their concerns? The drugs need to be taken long term (just like drugs for any other chronic condition). The new drugs are more expensive than the old drugs (just like new drugs for any other chronic condition). Lots of people will want to take them (just like highly effective drugs for any other chronic condition that has a significant quality-of-life or clinical impact). The U.K. recommended that they be covered only for 2 years (unlike drugs for any other chronic condition). And the Institute for Clinical and Economic Review (ICER) on which they lean heavily decided that $13,618 annually was too expensive for a medication that leads to sustained 15%-20% weight losses and those losses’ consequential benefits.

As a clinician working with patients who sustain those levels of weight loss, I find that conclusion confusing. Whether by way of lifestyle alone, or more often by way of lifestyle efforts plus medication or lifestyle efforts plus surgery, the benefits reported and seen with 15%-20% weight losses are almost uniformly huge. Patients are regularly seen discontinuing or reducing the dosage of multiple medications as a result of improvements to multiple weight-responsive comorbidities, and they also report objective benefits to mood, sleep, mobility, pain, and energy. Losing that much weight changes lives. Not to mention the impact that that degree of loss has on the primary prevention of so many diseases, including plausible reductions in many common cancers – reductions that have been shown to occur after surgery-related weight losses and for which there’s no plausible reason to imagine that they wouldn’t occur with pharmaceutical-related losses.

Are those discussions found in the NEJM op-ed or in the ICER report? Well, yes, sort of. However, in the NEJM op-ed, the word “prevention” isn’t used once, and unlike with oral hypoglycemics or antihypertensives, the authors state that with antiobesity medications, additional research is needed to determine whether medication-induced changes to A1c, blood pressure, and waist circumference would have clinical benefits: “Antiobesity medications have been shown to improve the surrogate end points of weight, glycated hemoglobin levels, systolic blood pressure, and waist circumference. Long-term studies are needed, however, to clarify how medication-induced changes in these surrogate markers translate to health outcomes.”

Primary prevention is mentioned in the ICER review, but in the “limitations” section where the authors explain that they didn’t include it in their modeling: “The long-term benefits of preventing other comorbidities including cancer, chronic kidney disease, osteoarthritis, and sleep apnea were not explicitly modeled in the base case.”

And they pretended that the impact on existing weight-responsive comorbidities mostly didn’t exist, too: “To limit the complexity of the cost-effectiveness model and to prevent double-counting of treatment benefits, we limited the long-term effects of treatments for weight management to cardiovascular risk and delays in the onset and/or diagnosis of diabetes mellitus.”

As far as cardiovascular disease (CVD) benefits go, you might have thought that it would be a slam dunk on that basis alone, at least according to a recent simple back-of-the-envelope math exercise presented at a recent American College of Cardiology conference, which applied the semaglutide treatment group weight changes in the STEP 1 trial to estimate the population impact on weight and obesity in 30- to 74-year-olds without prior CVD, and estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. By their accounting, semaglutide treatment in eligible American patients has the potential to prevent over 1.6 million CVD events over 10 years.

Finally, even putting aside ICER’s admittedly and exceedingly narrow base case, what lifestyle-alone studies could ICER possibly be comparing with drug efficacy? And what does “alone” mean? Does “alone” mean with a months- or years long interprofessional behavioral program? Does “alone” mean by way of diet books? Does “alone” mean by way of simply “moving more and eating less”? I’m not aware of robust studies demonstrating any long-term meaningful, predictable, reproducible, durable weight loss outcomes for any lifestyle-only approach, intensive or otherwise.

It’s difficult for me to imagine a situation in which a drug other than an antiobesity drug would be found to have too many benefits to include in your cost-effectiveness analysis but where you’d be comfortable to run that analysis anyhow, and then come out against the drug’s recommendation and fearmonger about its use.

But then again, systemic weight bias is a hell of a drug.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa. He disclosed ties with Constant Health and Novo Nordisk, and has shared opinions via Weighty Matters and social media.

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

The biased discourse and double standards around antiobesity glucagon-like peptide 1 (GLP-1) receptor agonists continue apace, most recently in The New England Journal of Medicine (NEJM) where some economists opined that their coverage would be disastrous for Medicare.

Among their concerns? The drugs need to be taken long term (just like drugs for any other chronic condition). The new drugs are more expensive than the old drugs (just like new drugs for any other chronic condition). Lots of people will want to take them (just like highly effective drugs for any other chronic condition that has a significant quality-of-life or clinical impact). The U.K. recommended that they be covered only for 2 years (unlike drugs for any other chronic condition). And the Institute for Clinical and Economic Review (ICER) on which they lean heavily decided that $13,618 annually was too expensive for a medication that leads to sustained 15%-20% weight losses and those losses’ consequential benefits.

As a clinician working with patients who sustain those levels of weight loss, I find that conclusion confusing. Whether by way of lifestyle alone, or more often by way of lifestyle efforts plus medication or lifestyle efforts plus surgery, the benefits reported and seen with 15%-20% weight losses are almost uniformly huge. Patients are regularly seen discontinuing or reducing the dosage of multiple medications as a result of improvements to multiple weight-responsive comorbidities, and they also report objective benefits to mood, sleep, mobility, pain, and energy. Losing that much weight changes lives. Not to mention the impact that that degree of loss has on the primary prevention of so many diseases, including plausible reductions in many common cancers – reductions that have been shown to occur after surgery-related weight losses and for which there’s no plausible reason to imagine that they wouldn’t occur with pharmaceutical-related losses.

Are those discussions found in the NEJM op-ed or in the ICER report? Well, yes, sort of. However, in the NEJM op-ed, the word “prevention” isn’t used once, and unlike with oral hypoglycemics or antihypertensives, the authors state that with antiobesity medications, additional research is needed to determine whether medication-induced changes to A1c, blood pressure, and waist circumference would have clinical benefits: “Antiobesity medications have been shown to improve the surrogate end points of weight, glycated hemoglobin levels, systolic blood pressure, and waist circumference. Long-term studies are needed, however, to clarify how medication-induced changes in these surrogate markers translate to health outcomes.”

Primary prevention is mentioned in the ICER review, but in the “limitations” section where the authors explain that they didn’t include it in their modeling: “The long-term benefits of preventing other comorbidities including cancer, chronic kidney disease, osteoarthritis, and sleep apnea were not explicitly modeled in the base case.”

And they pretended that the impact on existing weight-responsive comorbidities mostly didn’t exist, too: “To limit the complexity of the cost-effectiveness model and to prevent double-counting of treatment benefits, we limited the long-term effects of treatments for weight management to cardiovascular risk and delays in the onset and/or diagnosis of diabetes mellitus.”

As far as cardiovascular disease (CVD) benefits go, you might have thought that it would be a slam dunk on that basis alone, at least according to a recent simple back-of-the-envelope math exercise presented at a recent American College of Cardiology conference, which applied the semaglutide treatment group weight changes in the STEP 1 trial to estimate the population impact on weight and obesity in 30- to 74-year-olds without prior CVD, and estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. By their accounting, semaglutide treatment in eligible American patients has the potential to prevent over 1.6 million CVD events over 10 years.

Finally, even putting aside ICER’s admittedly and exceedingly narrow base case, what lifestyle-alone studies could ICER possibly be comparing with drug efficacy? And what does “alone” mean? Does “alone” mean with a months- or years long interprofessional behavioral program? Does “alone” mean by way of diet books? Does “alone” mean by way of simply “moving more and eating less”? I’m not aware of robust studies demonstrating any long-term meaningful, predictable, reproducible, durable weight loss outcomes for any lifestyle-only approach, intensive or otherwise.

It’s difficult for me to imagine a situation in which a drug other than an antiobesity drug would be found to have too many benefits to include in your cost-effectiveness analysis but where you’d be comfortable to run that analysis anyhow, and then come out against the drug’s recommendation and fearmonger about its use.

But then again, systemic weight bias is a hell of a drug.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa. He disclosed ties with Constant Health and Novo Nordisk, and has shared opinions via Weighty Matters and social media.

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

The biased discourse and double standards around antiobesity glucagon-like peptide 1 (GLP-1) receptor agonists continue apace, most recently in The New England Journal of Medicine (NEJM) where some economists opined that their coverage would be disastrous for Medicare.

Among their concerns? The drugs need to be taken long term (just like drugs for any other chronic condition). The new drugs are more expensive than the old drugs (just like new drugs for any other chronic condition). Lots of people will want to take them (just like highly effective drugs for any other chronic condition that has a significant quality-of-life or clinical impact). The U.K. recommended that they be covered only for 2 years (unlike drugs for any other chronic condition). And the Institute for Clinical and Economic Review (ICER) on which they lean heavily decided that $13,618 annually was too expensive for a medication that leads to sustained 15%-20% weight losses and those losses’ consequential benefits.

As a clinician working with patients who sustain those levels of weight loss, I find that conclusion confusing. Whether by way of lifestyle alone, or more often by way of lifestyle efforts plus medication or lifestyle efforts plus surgery, the benefits reported and seen with 15%-20% weight losses are almost uniformly huge. Patients are regularly seen discontinuing or reducing the dosage of multiple medications as a result of improvements to multiple weight-responsive comorbidities, and they also report objective benefits to mood, sleep, mobility, pain, and energy. Losing that much weight changes lives. Not to mention the impact that that degree of loss has on the primary prevention of so many diseases, including plausible reductions in many common cancers – reductions that have been shown to occur after surgery-related weight losses and for which there’s no plausible reason to imagine that they wouldn’t occur with pharmaceutical-related losses.

Are those discussions found in the NEJM op-ed or in the ICER report? Well, yes, sort of. However, in the NEJM op-ed, the word “prevention” isn’t used once, and unlike with oral hypoglycemics or antihypertensives, the authors state that with antiobesity medications, additional research is needed to determine whether medication-induced changes to A1c, blood pressure, and waist circumference would have clinical benefits: “Antiobesity medications have been shown to improve the surrogate end points of weight, glycated hemoglobin levels, systolic blood pressure, and waist circumference. Long-term studies are needed, however, to clarify how medication-induced changes in these surrogate markers translate to health outcomes.”

Primary prevention is mentioned in the ICER review, but in the “limitations” section where the authors explain that they didn’t include it in their modeling: “The long-term benefits of preventing other comorbidities including cancer, chronic kidney disease, osteoarthritis, and sleep apnea were not explicitly modeled in the base case.”

And they pretended that the impact on existing weight-responsive comorbidities mostly didn’t exist, too: “To limit the complexity of the cost-effectiveness model and to prevent double-counting of treatment benefits, we limited the long-term effects of treatments for weight management to cardiovascular risk and delays in the onset and/or diagnosis of diabetes mellitus.”

As far as cardiovascular disease (CVD) benefits go, you might have thought that it would be a slam dunk on that basis alone, at least according to a recent simple back-of-the-envelope math exercise presented at a recent American College of Cardiology conference, which applied the semaglutide treatment group weight changes in the STEP 1 trial to estimate the population impact on weight and obesity in 30- to 74-year-olds without prior CVD, and estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. By their accounting, semaglutide treatment in eligible American patients has the potential to prevent over 1.6 million CVD events over 10 years.

Finally, even putting aside ICER’s admittedly and exceedingly narrow base case, what lifestyle-alone studies could ICER possibly be comparing with drug efficacy? And what does “alone” mean? Does “alone” mean with a months- or years long interprofessional behavioral program? Does “alone” mean by way of diet books? Does “alone” mean by way of simply “moving more and eating less”? I’m not aware of robust studies demonstrating any long-term meaningful, predictable, reproducible, durable weight loss outcomes for any lifestyle-only approach, intensive or otherwise.

It’s difficult for me to imagine a situation in which a drug other than an antiobesity drug would be found to have too many benefits to include in your cost-effectiveness analysis but where you’d be comfortable to run that analysis anyhow, and then come out against the drug’s recommendation and fearmonger about its use.

But then again, systemic weight bias is a hell of a drug.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa. He disclosed ties with Constant Health and Novo Nordisk, and has shared opinions via Weighty Matters and social media.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

NEW ORLEANS – With the Asian population estimated to increase to 41 million by 2050 in the United States, expect the demand for experienced dermatologic care of patients with Asian skin to increase in the coming years, Hye Jin (Leah) Chung, MD, said at the annual meeting of the American Academy of Dermatology.

“Asians account for about 60% of the global population,” said Dr. Chung, assistant professor of dermatology at Harvard Medical School, and director of the Asian Skin Clinic at Beth Israel Deaconess Medical Center, Boston. Along with the estimate that Asians are expected to make up 25% of Canada’s population by 2036, “we will most likely encounter more Asian skin type patients in North America,” Dr. Chung said, noting that the Asian population “is very diverse, ranging from skin type 3 in Far East Asia to skin type 5 in India.”

Doug Brunk/MDedge News

During her presentation, she provided tips for treating hypertrophic scars and keloids in this patient population when intralesional corticosteroids fail. Typically, her first option is to combine an intralesional corticosteroid with 5-fluorouracil (5-FU), a pyrimidine analogue with antimetabolite activity. 5-FU “can cause cell apoptosis of endothelial cells and fibroblasts (which steroids cannot), cell cycle arrest, and TGF-beta [transforming growth factor beta]-induced COL1A2 transcription,” Dr. Chung said. The recommended ratio between 5-FU and steroids in the literature is variable, from a 9:1 ratio to a 1:1 ratio. “In my practice I do not inject more than 100 mg at a time,” she said. Several studies of this approach led by Asian investigators used weekly injections, “but that’s not practical in the U.S. I usually do monthly injections.”

A large systematic review and meta-analysis confirmed that the combination of intralesional triamcinolone acetonide and 5-FU achieved a better efficacy and fewer complications than triamcinolone alone for treating hypertrophic scars and keloids. Potential side effects from 5-FU injections include pain/pruritus, transient hyperpigmentation (especially in skin types 4-6), ulceration, teratogenicity, and transient alopecia.

A more recent meta-analysis comparing the efficacy of multiple drug injections for hypertrophic scars and keloids confirmed that the combination of triamcinolone and 5-FU was superior to bleomycin, verapamil, 5-FU alone, and triamcinolone alone. “And, there was no difference between 5-FU/steroid combination and botulinum toxin A,” Dr. Chung added. “Some parts of the world are using botulinum toxin with mixed results. Based on the amount of toxin required for keloids, this would be cost prohibitive in the U.S.”

Another approach to treating hypertrophic scars and keloids in Asian skin is laser-assisted drug delivery. “First, you can use a fractional ablative laser to create a hole in the epidermis and dermis,” Dr. Chung said. “Then you can apply the suspension topically to the holes. You can also use a steroid ointment or cream after laser treatment for drug delivery.”

Combining pulsed dye laser with steroid injections is another option. Pulsed dye lasers coagulate microvasculature within keloid tissue, “which can cause tissue hypoxia and can decrease growth factors or cytokines for fibrosis within the tissue,” Dr. Chung said. At the cellular level, pulsed dye laser alone can decrease connective tissue growth factor (CTGF), TGF-beta 1, proliferating cell nuclear antigen, and collagen III, and increases matrix metalloproteinase–13 (MMP-13), P53, ERK and p38 MAPK, apoptosis, blockade of AP-1 transcription, and cell cycle changes.

In 2004, plastic surgeons in Korea described a new approach for removing earlobe keloids, which they termed a “keloid fillet flap”. For the procedure, about 50% of the keloid margin is incised with a #15 scalpel blade. “Then you dissect the keloid from the surrounding tissue with a blade or curved scissors,” Dr. Chung said. “Next, you excise the keloid, so you have some dead space. After hemostasis you place the fillet flap to cover the wound. After you trim the redundant tissue, you can close it with epidermal sutures.”

In her clinical experience, she finds the fillet flap “very helpful for fast recovery” and it is associated with less pain. “Several studies have confirmed an excellent improvement of keloids, low recurrence rate, and rare side effects from a fillet flap and adjuvant intralesional corticosteroids. Occasionally, you may see flap necrosis but usually patients do well with topical antibiotics or petrolatum jelly.”

Dr. Chung also discussed her approach to treating papular scars in Asian patients. She described papular scars as underrecognized, anetoderma-like scars on the central face and trunk. “They comprise about 11% of all acne scars but up to 19% of patients with such scars may not recall a history of acne,” she said. Biopsies of papular scars reveal marked reduction or thinning of elastic fibers around hair follicles.

“Papular scars are difficult to treat,” she said. “If you have a conventional Er:YAG or CO₂ laser, you can create tiny holes within the scars,” she said, referring to studies on these approaches. Another treatment option is needle-guided radiofrequency, she noted.

Dr. Chung reported having no relevant financial disclosures.

NEW ORLEANS – With the Asian population estimated to increase to 41 million by 2050 in the United States, expect the demand for experienced dermatologic care of patients with Asian skin to increase in the coming years, Hye Jin (Leah) Chung, MD, said at the annual meeting of the American Academy of Dermatology.

“Asians account for about 60% of the global population,” said Dr. Chung, assistant professor of dermatology at Harvard Medical School, and director of the Asian Skin Clinic at Beth Israel Deaconess Medical Center, Boston. Along with the estimate that Asians are expected to make up 25% of Canada’s population by 2036, “we will most likely encounter more Asian skin type patients in North America,” Dr. Chung said, noting that the Asian population “is very diverse, ranging from skin type 3 in Far East Asia to skin type 5 in India.”

Doug Brunk/MDedge News

During her presentation, she provided tips for treating hypertrophic scars and keloids in this patient population when intralesional corticosteroids fail. Typically, her first option is to combine an intralesional corticosteroid with 5-fluorouracil (5-FU), a pyrimidine analogue with antimetabolite activity. 5-FU “can cause cell apoptosis of endothelial cells and fibroblasts (which steroids cannot), cell cycle arrest, and TGF-beta [transforming growth factor beta]-induced COL1A2 transcription,” Dr. Chung said. The recommended ratio between 5-FU and steroids in the literature is variable, from a 9:1 ratio to a 1:1 ratio. “In my practice I do not inject more than 100 mg at a time,” she said. Several studies of this approach led by Asian investigators used weekly injections, “but that’s not practical in the U.S. I usually do monthly injections.”

A large systematic review and meta-analysis confirmed that the combination of intralesional triamcinolone acetonide and 5-FU achieved a better efficacy and fewer complications than triamcinolone alone for treating hypertrophic scars and keloids. Potential side effects from 5-FU injections include pain/pruritus, transient hyperpigmentation (especially in skin types 4-6), ulceration, teratogenicity, and transient alopecia.

A more recent meta-analysis comparing the efficacy of multiple drug injections for hypertrophic scars and keloids confirmed that the combination of triamcinolone and 5-FU was superior to bleomycin, verapamil, 5-FU alone, and triamcinolone alone. “And, there was no difference between 5-FU/steroid combination and botulinum toxin A,” Dr. Chung added. “Some parts of the world are using botulinum toxin with mixed results. Based on the amount of toxin required for keloids, this would be cost prohibitive in the U.S.”

Another approach to treating hypertrophic scars and keloids in Asian skin is laser-assisted drug delivery. “First, you can use a fractional ablative laser to create a hole in the epidermis and dermis,” Dr. Chung said. “Then you can apply the suspension topically to the holes. You can also use a steroid ointment or cream after laser treatment for drug delivery.”

Combining pulsed dye laser with steroid injections is another option. Pulsed dye lasers coagulate microvasculature within keloid tissue, “which can cause tissue hypoxia and can decrease growth factors or cytokines for fibrosis within the tissue,” Dr. Chung said. At the cellular level, pulsed dye laser alone can decrease connective tissue growth factor (CTGF), TGF-beta 1, proliferating cell nuclear antigen, and collagen III, and increases matrix metalloproteinase–13 (MMP-13), P53, ERK and p38 MAPK, apoptosis, blockade of AP-1 transcription, and cell cycle changes.

In 2004, plastic surgeons in Korea described a new approach for removing earlobe keloids, which they termed a “keloid fillet flap”. For the procedure, about 50% of the keloid margin is incised with a #15 scalpel blade. “Then you dissect the keloid from the surrounding tissue with a blade or curved scissors,” Dr. Chung said. “Next, you excise the keloid, so you have some dead space. After hemostasis you place the fillet flap to cover the wound. After you trim the redundant tissue, you can close it with epidermal sutures.”

In her clinical experience, she finds the fillet flap “very helpful for fast recovery” and it is associated with less pain. “Several studies have confirmed an excellent improvement of keloids, low recurrence rate, and rare side effects from a fillet flap and adjuvant intralesional corticosteroids. Occasionally, you may see flap necrosis but usually patients do well with topical antibiotics or petrolatum jelly.”

Dr. Chung also discussed her approach to treating papular scars in Asian patients. She described papular scars as underrecognized, anetoderma-like scars on the central face and trunk. “They comprise about 11% of all acne scars but up to 19% of patients with such scars may not recall a history of acne,” she said. Biopsies of papular scars reveal marked reduction or thinning of elastic fibers around hair follicles.

“Papular scars are difficult to treat,” she said. “If you have a conventional Er:YAG or CO₂ laser, you can create tiny holes within the scars,” she said, referring to studies on these approaches. Another treatment option is needle-guided radiofrequency, she noted.

Dr. Chung reported having no relevant financial disclosures.

NEW ORLEANS – With the Asian population estimated to increase to 41 million by 2050 in the United States, expect the demand for experienced dermatologic care of patients with Asian skin to increase in the coming years, Hye Jin (Leah) Chung, MD, said at the annual meeting of the American Academy of Dermatology.

“Asians account for about 60% of the global population,” said Dr. Chung, assistant professor of dermatology at Harvard Medical School, and director of the Asian Skin Clinic at Beth Israel Deaconess Medical Center, Boston. Along with the estimate that Asians are expected to make up 25% of Canada’s population by 2036, “we will most likely encounter more Asian skin type patients in North America,” Dr. Chung said, noting that the Asian population “is very diverse, ranging from skin type 3 in Far East Asia to skin type 5 in India.”

Doug Brunk/MDedge News

During her presentation, she provided tips for treating hypertrophic scars and keloids in this patient population when intralesional corticosteroids fail. Typically, her first option is to combine an intralesional corticosteroid with 5-fluorouracil (5-FU), a pyrimidine analogue with antimetabolite activity. 5-FU “can cause cell apoptosis of endothelial cells and fibroblasts (which steroids cannot), cell cycle arrest, and TGF-beta [transforming growth factor beta]-induced COL1A2 transcription,” Dr. Chung said. The recommended ratio between 5-FU and steroids in the literature is variable, from a 9:1 ratio to a 1:1 ratio. “In my practice I do not inject more than 100 mg at a time,” she said. Several studies of this approach led by Asian investigators used weekly injections, “but that’s not practical in the U.S. I usually do monthly injections.”

A large systematic review and meta-analysis confirmed that the combination of intralesional triamcinolone acetonide and 5-FU achieved a better efficacy and fewer complications than triamcinolone alone for treating hypertrophic scars and keloids. Potential side effects from 5-FU injections include pain/pruritus, transient hyperpigmentation (especially in skin types 4-6), ulceration, teratogenicity, and transient alopecia.

A more recent meta-analysis comparing the efficacy of multiple drug injections for hypertrophic scars and keloids confirmed that the combination of triamcinolone and 5-FU was superior to bleomycin, verapamil, 5-FU alone, and triamcinolone alone. “And, there was no difference between 5-FU/steroid combination and botulinum toxin A,” Dr. Chung added. “Some parts of the world are using botulinum toxin with mixed results. Based on the amount of toxin required for keloids, this would be cost prohibitive in the U.S.”

Another approach to treating hypertrophic scars and keloids in Asian skin is laser-assisted drug delivery. “First, you can use a fractional ablative laser to create a hole in the epidermis and dermis,” Dr. Chung said. “Then you can apply the suspension topically to the holes. You can also use a steroid ointment or cream after laser treatment for drug delivery.”

Combining pulsed dye laser with steroid injections is another option. Pulsed dye lasers coagulate microvasculature within keloid tissue, “which can cause tissue hypoxia and can decrease growth factors or cytokines for fibrosis within the tissue,” Dr. Chung said. At the cellular level, pulsed dye laser alone can decrease connective tissue growth factor (CTGF), TGF-beta 1, proliferating cell nuclear antigen, and collagen III, and increases matrix metalloproteinase–13 (MMP-13), P53, ERK and p38 MAPK, apoptosis, blockade of AP-1 transcription, and cell cycle changes.

In 2004, plastic surgeons in Korea described a new approach for removing earlobe keloids, which they termed a “keloid fillet flap”. For the procedure, about 50% of the keloid margin is incised with a #15 scalpel blade. “Then you dissect the keloid from the surrounding tissue with a blade or curved scissors,” Dr. Chung said. “Next, you excise the keloid, so you have some dead space. After hemostasis you place the fillet flap to cover the wound. After you trim the redundant tissue, you can close it with epidermal sutures.”

In her clinical experience, she finds the fillet flap “very helpful for fast recovery” and it is associated with less pain. “Several studies have confirmed an excellent improvement of keloids, low recurrence rate, and rare side effects from a fillet flap and adjuvant intralesional corticosteroids. Occasionally, you may see flap necrosis but usually patients do well with topical antibiotics or petrolatum jelly.”

Dr. Chung also discussed her approach to treating papular scars in Asian patients. She described papular scars as underrecognized, anetoderma-like scars on the central face and trunk. “They comprise about 11% of all acne scars but up to 19% of patients with such scars may not recall a history of acne,” she said. Biopsies of papular scars reveal marked reduction or thinning of elastic fibers around hair follicles.

“Papular scars are difficult to treat,” she said. “If you have a conventional Er:YAG or CO₂ laser, you can create tiny holes within the scars,” she said, referring to studies on these approaches. Another treatment option is needle-guided radiofrequency, she noted.

Dr. Chung reported having no relevant financial disclosures.

Recent trial evidence has failed to show a cardiovascular benefit to treating high triglycerides. The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?

There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.

There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.

But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
 

Independent cardiovascular risk factor?

If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?

Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.

But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.

Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.

Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
 

The pre- vs. post-statin era

In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.

The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.

Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.

You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.

If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.

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

Recent trial evidence has failed to show a cardiovascular benefit to treating high triglycerides. The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?

There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.

There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.

But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
 

Independent cardiovascular risk factor?

If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?

Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.

But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.

Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.

Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
 

The pre- vs. post-statin era

In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.

The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.

Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.

You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.

If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.

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

Recent trial evidence has failed to show a cardiovascular benefit to treating high triglycerides. The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?

There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.

There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.

But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
 

Independent cardiovascular risk factor?

If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?

Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.

But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.

Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.

Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
 

The pre- vs. post-statin era

In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.

The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.

Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.

You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.

If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.

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