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Mercury and other risks of cosmetic skin lighteners
Skin hyperpigmentation – whether it is caused by postinflammatory hyperpigmentation from acne or trauma to the skin, melasma, autoimmune disorders, or disorders of pigmentation – is a condition where treatment is commonly sought after in dermatology offices. Topical products used to fade hyperpigmented areas of the skin have long been used around the world, and because of safety concerns, regulations aimed at reducing potential harm or adverse effects caused by certain ingredients in these products are increasing in different countries.
For example, while extremely effective at treating most forms of hyperpigmentation, hydroquinone has been definitively linked to ochronosis, kojic acid has been linked to contact dermatitis in humans, and acid peels and retinoids are associated with irritant dermatitis, disruption of the skin barrier, and photosensitivity. In animal studies, licorice root extract has been linked to endocrine and other organ system irregularities.
Kojic acid was banned in Japan in 2003, and subsequently in South Korea and Switzerland because of concerns over animal studies indicating that its fungal metabolite might be carcinogenic (. Hydroquinone is classified as a drug and has been banned for use in cosmetic products in Japan, the European Union, Australia, and several African nations since at least 2006 because of concerns over adrenal gland dysregulation and high levels of mercury in hydroquinone products in those countries. In Africa specifically, South Africa banned all but 2% hydroquinone in 1983, the Ivory Coast banned all skin whitening creams in 2015, and in 2016, Ghana initiated a ban on certain skin products containing hydroquinone.
The United States followed suit in February 2020 with the Food and Drug Administration introducing a ban on all OTC hydroquinone-containing products because of concerns over carcinogenicity in animal studies (which has not been shown in human studies to date). The “Coronavirus Aid, Relief, and Economic Security” (CARES) Act signed in March 2020 then made the changes effective by halting the sale of OTC hydroquinone products in the United States as of September 2020.
Mercury concerns
Despite these bans, hydroquinone continues to be sold in cosmetics and OTC products around the world and online. And despite being banned or limited in these products, in particular. Mercury has been used in cosmetic products as a skin lightening agent (on its own) and as a preservative.
Mercury has been shown to be carcinogenic, neurotoxic, as well as cytotoxic to the renal and endocrine systems, causes reproductive toxicity, and may be bioaccumulative in wildlife and humans. There is particular concern regarding the risks of exposure in pregnant women and babies because of potential harm to the developing brain and nervous system. Initial signs and symptoms of mercury poisoning include irritability, shyness, tremors, changes in vision or hearing, memory problems, depression, numbness and tingling in the hands, feet, or around the mouth.
Organizations such as the Zero Mercury Working Group (ZMWG) – an international coalition of public interest environmental and health nongovernmental organizations from more than 55 countries, focused on eliminating the use, release, and exposure to mercury – have been working to help ensure safety and mercury levels are below the threshold deemed allowable in hydroquinone-containing products.
On March 10, the ZMWG published the results of a new study demonstrating that skin lighteners containing mercury are still being sold online, despite bans and safety concerns. Ebay, Amazon, Shopee, Jiji, and Flipkart are among the websites still selling high mercury–containing skin lightener products. Some of them were the same offenders selling the banned products in 2019. Of the 271 online products tested from 17 countries, nearly half contained over 1 ppm of mercury, which is the legal limit that has been established by most governments and the Minamata Convention on Mercury. Based on their packaging, the majority of these products were manufactured in Asia, most often in Pakistan (43%), Thailand (8%), China (6%), and Taiwan (4%), according to the report.
In ZMWG’s prior publications, mercury concentrations reported in some of these products ranged from 93 ppm to over 16,000 ppm. Even higher concentrations have been reported by other entities. And according to a World Health Organization November 2019 report, mercury-containing skin lightening products have been manufactured in many countries and areas, including Bangladesh, China, Dominican Republic Hong Kong SAR (China), Jamaica, Lebanon, Malaysia, Mexico, Pakistan, Philippines, Republic of Korea, Thailand, and the United States. According to the ZMWG, 137 countries have committed to the Minamata Convention to phase out and limit mercury, including in cosmetics.
Despite bans on some of these products, consumers in the United States and other countries with bans and restrictions are still at risk of exposure to mercury-containing skin lighteners because of online sales. Hopefully, the work of the ZMWG and similar entities will continue to help limit potentially harmful exposures to mercury, while maintaining access to safe and effective methods to treat hyperpigmentation.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
Skin hyperpigmentation – whether it is caused by postinflammatory hyperpigmentation from acne or trauma to the skin, melasma, autoimmune disorders, or disorders of pigmentation – is a condition where treatment is commonly sought after in dermatology offices. Topical products used to fade hyperpigmented areas of the skin have long been used around the world, and because of safety concerns, regulations aimed at reducing potential harm or adverse effects caused by certain ingredients in these products are increasing in different countries.
For example, while extremely effective at treating most forms of hyperpigmentation, hydroquinone has been definitively linked to ochronosis, kojic acid has been linked to contact dermatitis in humans, and acid peels and retinoids are associated with irritant dermatitis, disruption of the skin barrier, and photosensitivity. In animal studies, licorice root extract has been linked to endocrine and other organ system irregularities.
Kojic acid was banned in Japan in 2003, and subsequently in South Korea and Switzerland because of concerns over animal studies indicating that its fungal metabolite might be carcinogenic (. Hydroquinone is classified as a drug and has been banned for use in cosmetic products in Japan, the European Union, Australia, and several African nations since at least 2006 because of concerns over adrenal gland dysregulation and high levels of mercury in hydroquinone products in those countries. In Africa specifically, South Africa banned all but 2% hydroquinone in 1983, the Ivory Coast banned all skin whitening creams in 2015, and in 2016, Ghana initiated a ban on certain skin products containing hydroquinone.
The United States followed suit in February 2020 with the Food and Drug Administration introducing a ban on all OTC hydroquinone-containing products because of concerns over carcinogenicity in animal studies (which has not been shown in human studies to date). The “Coronavirus Aid, Relief, and Economic Security” (CARES) Act signed in March 2020 then made the changes effective by halting the sale of OTC hydroquinone products in the United States as of September 2020.
Mercury concerns
Despite these bans, hydroquinone continues to be sold in cosmetics and OTC products around the world and online. And despite being banned or limited in these products, in particular. Mercury has been used in cosmetic products as a skin lightening agent (on its own) and as a preservative.
Mercury has been shown to be carcinogenic, neurotoxic, as well as cytotoxic to the renal and endocrine systems, causes reproductive toxicity, and may be bioaccumulative in wildlife and humans. There is particular concern regarding the risks of exposure in pregnant women and babies because of potential harm to the developing brain and nervous system. Initial signs and symptoms of mercury poisoning include irritability, shyness, tremors, changes in vision or hearing, memory problems, depression, numbness and tingling in the hands, feet, or around the mouth.
Organizations such as the Zero Mercury Working Group (ZMWG) – an international coalition of public interest environmental and health nongovernmental organizations from more than 55 countries, focused on eliminating the use, release, and exposure to mercury – have been working to help ensure safety and mercury levels are below the threshold deemed allowable in hydroquinone-containing products.
On March 10, the ZMWG published the results of a new study demonstrating that skin lighteners containing mercury are still being sold online, despite bans and safety concerns. Ebay, Amazon, Shopee, Jiji, and Flipkart are among the websites still selling high mercury–containing skin lightener products. Some of them were the same offenders selling the banned products in 2019. Of the 271 online products tested from 17 countries, nearly half contained over 1 ppm of mercury, which is the legal limit that has been established by most governments and the Minamata Convention on Mercury. Based on their packaging, the majority of these products were manufactured in Asia, most often in Pakistan (43%), Thailand (8%), China (6%), and Taiwan (4%), according to the report.
In ZMWG’s prior publications, mercury concentrations reported in some of these products ranged from 93 ppm to over 16,000 ppm. Even higher concentrations have been reported by other entities. And according to a World Health Organization November 2019 report, mercury-containing skin lightening products have been manufactured in many countries and areas, including Bangladesh, China, Dominican Republic Hong Kong SAR (China), Jamaica, Lebanon, Malaysia, Mexico, Pakistan, Philippines, Republic of Korea, Thailand, and the United States. According to the ZMWG, 137 countries have committed to the Minamata Convention to phase out and limit mercury, including in cosmetics.
Despite bans on some of these products, consumers in the United States and other countries with bans and restrictions are still at risk of exposure to mercury-containing skin lighteners because of online sales. Hopefully, the work of the ZMWG and similar entities will continue to help limit potentially harmful exposures to mercury, while maintaining access to safe and effective methods to treat hyperpigmentation.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
Skin hyperpigmentation – whether it is caused by postinflammatory hyperpigmentation from acne or trauma to the skin, melasma, autoimmune disorders, or disorders of pigmentation – is a condition where treatment is commonly sought after in dermatology offices. Topical products used to fade hyperpigmented areas of the skin have long been used around the world, and because of safety concerns, regulations aimed at reducing potential harm or adverse effects caused by certain ingredients in these products are increasing in different countries.
For example, while extremely effective at treating most forms of hyperpigmentation, hydroquinone has been definitively linked to ochronosis, kojic acid has been linked to contact dermatitis in humans, and acid peels and retinoids are associated with irritant dermatitis, disruption of the skin barrier, and photosensitivity. In animal studies, licorice root extract has been linked to endocrine and other organ system irregularities.
Kojic acid was banned in Japan in 2003, and subsequently in South Korea and Switzerland because of concerns over animal studies indicating that its fungal metabolite might be carcinogenic (. Hydroquinone is classified as a drug and has been banned for use in cosmetic products in Japan, the European Union, Australia, and several African nations since at least 2006 because of concerns over adrenal gland dysregulation and high levels of mercury in hydroquinone products in those countries. In Africa specifically, South Africa banned all but 2% hydroquinone in 1983, the Ivory Coast banned all skin whitening creams in 2015, and in 2016, Ghana initiated a ban on certain skin products containing hydroquinone.
The United States followed suit in February 2020 with the Food and Drug Administration introducing a ban on all OTC hydroquinone-containing products because of concerns over carcinogenicity in animal studies (which has not been shown in human studies to date). The “Coronavirus Aid, Relief, and Economic Security” (CARES) Act signed in March 2020 then made the changes effective by halting the sale of OTC hydroquinone products in the United States as of September 2020.
Mercury concerns
Despite these bans, hydroquinone continues to be sold in cosmetics and OTC products around the world and online. And despite being banned or limited in these products, in particular. Mercury has been used in cosmetic products as a skin lightening agent (on its own) and as a preservative.
Mercury has been shown to be carcinogenic, neurotoxic, as well as cytotoxic to the renal and endocrine systems, causes reproductive toxicity, and may be bioaccumulative in wildlife and humans. There is particular concern regarding the risks of exposure in pregnant women and babies because of potential harm to the developing brain and nervous system. Initial signs and symptoms of mercury poisoning include irritability, shyness, tremors, changes in vision or hearing, memory problems, depression, numbness and tingling in the hands, feet, or around the mouth.
Organizations such as the Zero Mercury Working Group (ZMWG) – an international coalition of public interest environmental and health nongovernmental organizations from more than 55 countries, focused on eliminating the use, release, and exposure to mercury – have been working to help ensure safety and mercury levels are below the threshold deemed allowable in hydroquinone-containing products.
On March 10, the ZMWG published the results of a new study demonstrating that skin lighteners containing mercury are still being sold online, despite bans and safety concerns. Ebay, Amazon, Shopee, Jiji, and Flipkart are among the websites still selling high mercury–containing skin lightener products. Some of them were the same offenders selling the banned products in 2019. Of the 271 online products tested from 17 countries, nearly half contained over 1 ppm of mercury, which is the legal limit that has been established by most governments and the Minamata Convention on Mercury. Based on their packaging, the majority of these products were manufactured in Asia, most often in Pakistan (43%), Thailand (8%), China (6%), and Taiwan (4%), according to the report.
In ZMWG’s prior publications, mercury concentrations reported in some of these products ranged from 93 ppm to over 16,000 ppm. Even higher concentrations have been reported by other entities. And according to a World Health Organization November 2019 report, mercury-containing skin lightening products have been manufactured in many countries and areas, including Bangladesh, China, Dominican Republic Hong Kong SAR (China), Jamaica, Lebanon, Malaysia, Mexico, Pakistan, Philippines, Republic of Korea, Thailand, and the United States. According to the ZMWG, 137 countries have committed to the Minamata Convention to phase out and limit mercury, including in cosmetics.
Despite bans on some of these products, consumers in the United States and other countries with bans and restrictions are still at risk of exposure to mercury-containing skin lighteners because of online sales. Hopefully, the work of the ZMWG and similar entities will continue to help limit potentially harmful exposures to mercury, while maintaining access to safe and effective methods to treat hyperpigmentation.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
A 31-year-old female presented with a burning rash on upper arms, groin, and axillae
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
Betamethasone cream did not alleviate symptoms.
Don’t drink calories: Artificial sweeteners beat sugar in new analysis
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Diagnosing adolescent ADHD
Pediatricians are increasingly expert in the assessment and treatment of attention-deficit/hyperactivity disorder. But what do you do when adolescents present to your office saying they think they have ADHD? While ADHD is a common and treatable disorder of youth, it is important to take special care when assessing an adolescent. Difficulties with attention and concentration are common symptoms for many different challenges of adolescence, and for ADHD to be the underlying cause, those symptoms must have started prior to adolescence (according to DSM-5, prior to the age of 12). When your adolescent patients or their parents come to your office complaining of inattention, it is important to consider the full range of possible explanations.
Sleep
We have written in this column previously about the challenges that adolescents face in getting adequate sleep consistently. Teenagers, on average, need more than 9 hours of sleep nightly and American teenagers get fewer than 6. This mismatch is because of physiologic shifts that move their natural sleep onset time significantly later, while school still starts early. It’s often compounded by other demands on their time, including homework, extracurricular activities, and the gravitational pull of social connections. Independent teenagers make their own decisions about how to manage their time and may feel sleep is optional, or manage their fatigue with naps and caffeine, both of which will further compromise the quality and efficiency of sleep.
Chronic sleep deprivation will present with difficulties with focus, attention, memory, and cognitive performance. Treatment of this problem with stimulants is likely to make the underlying poor sleep habits even worse. When your patient presents complaining of difficulty concentrating and worsening school performance, be sure to start with a thorough sleep history, and always provide guidance about the body’s need for sleep and healthy sleep habits.
Anxiety
Anxiety disorders are the most common psychiatric illnesses of youth, with estimates of as many as 30% of children and adolescents experiencing one. The true prevalence of ADHD is estimated to be about 4% of the population. Whether social phobia, generalized anxiety disorder, or even posttraumatic stress disorder, anxiety disorders interfere with attention as ruminative worry tends to distract those experiencing it. It can also affect attention and focus indirectly by interfering with restful sleep. Anxiety disorders can be difficult to identify, as the sufferers typically internalize their symptoms. But inquire about specific worries (such as speaking in front of others, meeting new people, or an illness or accident striking themselves or a loved one) and how much time they take up. Explore if worries fill their thoughts during quiet or downtime, and explore more about their worries. You may use a screening instrument such as the Pediatric Symptom Checklist or the SCARED, both of which will indicate a likely problem with anxiety. While it is possible to have comorbid ADHD with an anxiety disorder, the anxiety disorder will likely worsen with stimulants and should be treated first. These are usually curable illnesses and you may find that remission of anxiety symptoms resolves the attentional problems.
Depression
Mood disorders are less common than anxiety disorders in youth, but far more prevalent than ADHD. And depression is usually marked by serious difficulty concentrating across settings (including for things that were previously very interesting). A sullen teenager who is deeply self-critical about school performance would benefit from exploration of associated changes in mood, interests, energy, appetite, sleep, and for feelings of worthlessness, guilt, and suicidal thoughts. The PHQ9A is a simple, free screening instrument that is reasonable to use with every sick visit (and well-check) with your adolescent patients, given the risks of undetected and untreated depression. If your patient presents complaining of poor school performance, always screen for depression. As with anxiety disorders, comorbid ADHD is possible, but it is always recommended to treat the mood disorder first and then to assess for residual ADHD symptoms once the mood disorder is in remission.
Substance abuse
Adolescence is a time of exploration, and drug and alcohol use is common. While attentional impairment will happen with intoxication, occasional or rare use should not lead to consistent impairment in school. But when parents are more worried than their children about a significant change in school performance, it is important to screen for substance abuse. A child with a secret substance use disorder will often present with behavioral changes and deteriorating school performance and might deny any drug or alcohol use to parents. Indeed, stimulants have some street value and some patients may be seeking a stimulant prescription to sell or trade for other drugs. Regular marijuana use may present with only deteriorating school performance and no irritability or other noticeable behavioral changes. Marijuana is seen as safe and even healthy by many teenagers (and even many parents), and some youth may be using it recreationally or to manage difficulties with sleep, anxiety, or mood symptoms.
But there is compelling evidence that marijuana use causes cognitive impairment, including difficulty with sustaining attention, short-term memory, and processing speed, for as long as 24 hours after use. If a teenager is using marijuana daily after school, it is certainly going to interfere, in a dose-dependent manner, with attention and cognitive function. Sustained heavy use can lead to permanent cognitive deficits. It can also trigger or worsen anxiety or mood symptoms (contrary to much popular opinion).
Gathering a thorough substance use history is essential when assessing a teenager for difficulties with focus or attention, especially when these are accompanied by change in behavior and school performance. Remember, it is critical to interview these children without their parents present to invite them to be forthcoming with you.
History
While true ADHD should have been present throughout childhood, it is possible that the symptoms have become noticeable only in adolescence. For patients with very high intelligence and lower levels of impulsivity and hyperactivity, they might easily have “flown under the radar” during their elementary and even middle school years. Their difficulties with attention and focus might become apparent only when the volume and difficulty of schoolwork both are great enough that their intelligence is not enough to get good grades. That is, their problems with executive function, prioritizing, shifting sets, and completing tasks in a timely way make it impossible to keep up good grades when the work gets harder.
Your history should reveal a long history of dreaminess or distractibility, a tendency to lose and forget things, and the other symptoms of inattention. Did they often seem to not be listening when they were younger? Forget to hand in homework? Leave chores unfinished? Leave messes behind everywhere they went? These will not be definitive, but they do reassure that symptoms may have been present for a long time, even if school performance was considered fine until the workload got too large. If such problems were not present before puberty, consider whether a subtle learning disability could be impairing them as they face more challenging academic subjects.
If you have ruled out anxiety, mood, and substance use concerns, and helped them to address a sleep deficit, then you can proceed. It is worthwhile to get Vanderbilt Assessments as you would for a younger child. If they meet criteria, discuss the risks and benefits of medication, executive skills coaching, and environmental adjustments (extra time for tests, a less stimulating environment) that can help them explore academic challenges without the discouragement that ADHD can bring.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Pediatricians are increasingly expert in the assessment and treatment of attention-deficit/hyperactivity disorder. But what do you do when adolescents present to your office saying they think they have ADHD? While ADHD is a common and treatable disorder of youth, it is important to take special care when assessing an adolescent. Difficulties with attention and concentration are common symptoms for many different challenges of adolescence, and for ADHD to be the underlying cause, those symptoms must have started prior to adolescence (according to DSM-5, prior to the age of 12). When your adolescent patients or their parents come to your office complaining of inattention, it is important to consider the full range of possible explanations.
Sleep
We have written in this column previously about the challenges that adolescents face in getting adequate sleep consistently. Teenagers, on average, need more than 9 hours of sleep nightly and American teenagers get fewer than 6. This mismatch is because of physiologic shifts that move their natural sleep onset time significantly later, while school still starts early. It’s often compounded by other demands on their time, including homework, extracurricular activities, and the gravitational pull of social connections. Independent teenagers make their own decisions about how to manage their time and may feel sleep is optional, or manage their fatigue with naps and caffeine, both of which will further compromise the quality and efficiency of sleep.
Chronic sleep deprivation will present with difficulties with focus, attention, memory, and cognitive performance. Treatment of this problem with stimulants is likely to make the underlying poor sleep habits even worse. When your patient presents complaining of difficulty concentrating and worsening school performance, be sure to start with a thorough sleep history, and always provide guidance about the body’s need for sleep and healthy sleep habits.
Anxiety
Anxiety disorders are the most common psychiatric illnesses of youth, with estimates of as many as 30% of children and adolescents experiencing one. The true prevalence of ADHD is estimated to be about 4% of the population. Whether social phobia, generalized anxiety disorder, or even posttraumatic stress disorder, anxiety disorders interfere with attention as ruminative worry tends to distract those experiencing it. It can also affect attention and focus indirectly by interfering with restful sleep. Anxiety disorders can be difficult to identify, as the sufferers typically internalize their symptoms. But inquire about specific worries (such as speaking in front of others, meeting new people, or an illness or accident striking themselves or a loved one) and how much time they take up. Explore if worries fill their thoughts during quiet or downtime, and explore more about their worries. You may use a screening instrument such as the Pediatric Symptom Checklist or the SCARED, both of which will indicate a likely problem with anxiety. While it is possible to have comorbid ADHD with an anxiety disorder, the anxiety disorder will likely worsen with stimulants and should be treated first. These are usually curable illnesses and you may find that remission of anxiety symptoms resolves the attentional problems.
Depression
Mood disorders are less common than anxiety disorders in youth, but far more prevalent than ADHD. And depression is usually marked by serious difficulty concentrating across settings (including for things that were previously very interesting). A sullen teenager who is deeply self-critical about school performance would benefit from exploration of associated changes in mood, interests, energy, appetite, sleep, and for feelings of worthlessness, guilt, and suicidal thoughts. The PHQ9A is a simple, free screening instrument that is reasonable to use with every sick visit (and well-check) with your adolescent patients, given the risks of undetected and untreated depression. If your patient presents complaining of poor school performance, always screen for depression. As with anxiety disorders, comorbid ADHD is possible, but it is always recommended to treat the mood disorder first and then to assess for residual ADHD symptoms once the mood disorder is in remission.
Substance abuse
Adolescence is a time of exploration, and drug and alcohol use is common. While attentional impairment will happen with intoxication, occasional or rare use should not lead to consistent impairment in school. But when parents are more worried than their children about a significant change in school performance, it is important to screen for substance abuse. A child with a secret substance use disorder will often present with behavioral changes and deteriorating school performance and might deny any drug or alcohol use to parents. Indeed, stimulants have some street value and some patients may be seeking a stimulant prescription to sell or trade for other drugs. Regular marijuana use may present with only deteriorating school performance and no irritability or other noticeable behavioral changes. Marijuana is seen as safe and even healthy by many teenagers (and even many parents), and some youth may be using it recreationally or to manage difficulties with sleep, anxiety, or mood symptoms.
But there is compelling evidence that marijuana use causes cognitive impairment, including difficulty with sustaining attention, short-term memory, and processing speed, for as long as 24 hours after use. If a teenager is using marijuana daily after school, it is certainly going to interfere, in a dose-dependent manner, with attention and cognitive function. Sustained heavy use can lead to permanent cognitive deficits. It can also trigger or worsen anxiety or mood symptoms (contrary to much popular opinion).
Gathering a thorough substance use history is essential when assessing a teenager for difficulties with focus or attention, especially when these are accompanied by change in behavior and school performance. Remember, it is critical to interview these children without their parents present to invite them to be forthcoming with you.
History
While true ADHD should have been present throughout childhood, it is possible that the symptoms have become noticeable only in adolescence. For patients with very high intelligence and lower levels of impulsivity and hyperactivity, they might easily have “flown under the radar” during their elementary and even middle school years. Their difficulties with attention and focus might become apparent only when the volume and difficulty of schoolwork both are great enough that their intelligence is not enough to get good grades. That is, their problems with executive function, prioritizing, shifting sets, and completing tasks in a timely way make it impossible to keep up good grades when the work gets harder.
Your history should reveal a long history of dreaminess or distractibility, a tendency to lose and forget things, and the other symptoms of inattention. Did they often seem to not be listening when they were younger? Forget to hand in homework? Leave chores unfinished? Leave messes behind everywhere they went? These will not be definitive, but they do reassure that symptoms may have been present for a long time, even if school performance was considered fine until the workload got too large. If such problems were not present before puberty, consider whether a subtle learning disability could be impairing them as they face more challenging academic subjects.
If you have ruled out anxiety, mood, and substance use concerns, and helped them to address a sleep deficit, then you can proceed. It is worthwhile to get Vanderbilt Assessments as you would for a younger child. If they meet criteria, discuss the risks and benefits of medication, executive skills coaching, and environmental adjustments (extra time for tests, a less stimulating environment) that can help them explore academic challenges without the discouragement that ADHD can bring.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Pediatricians are increasingly expert in the assessment and treatment of attention-deficit/hyperactivity disorder. But what do you do when adolescents present to your office saying they think they have ADHD? While ADHD is a common and treatable disorder of youth, it is important to take special care when assessing an adolescent. Difficulties with attention and concentration are common symptoms for many different challenges of adolescence, and for ADHD to be the underlying cause, those symptoms must have started prior to adolescence (according to DSM-5, prior to the age of 12). When your adolescent patients or their parents come to your office complaining of inattention, it is important to consider the full range of possible explanations.
Sleep
We have written in this column previously about the challenges that adolescents face in getting adequate sleep consistently. Teenagers, on average, need more than 9 hours of sleep nightly and American teenagers get fewer than 6. This mismatch is because of physiologic shifts that move their natural sleep onset time significantly later, while school still starts early. It’s often compounded by other demands on their time, including homework, extracurricular activities, and the gravitational pull of social connections. Independent teenagers make their own decisions about how to manage their time and may feel sleep is optional, or manage their fatigue with naps and caffeine, both of which will further compromise the quality and efficiency of sleep.
Chronic sleep deprivation will present with difficulties with focus, attention, memory, and cognitive performance. Treatment of this problem with stimulants is likely to make the underlying poor sleep habits even worse. When your patient presents complaining of difficulty concentrating and worsening school performance, be sure to start with a thorough sleep history, and always provide guidance about the body’s need for sleep and healthy sleep habits.
Anxiety
Anxiety disorders are the most common psychiatric illnesses of youth, with estimates of as many as 30% of children and adolescents experiencing one. The true prevalence of ADHD is estimated to be about 4% of the population. Whether social phobia, generalized anxiety disorder, or even posttraumatic stress disorder, anxiety disorders interfere with attention as ruminative worry tends to distract those experiencing it. It can also affect attention and focus indirectly by interfering with restful sleep. Anxiety disorders can be difficult to identify, as the sufferers typically internalize their symptoms. But inquire about specific worries (such as speaking in front of others, meeting new people, or an illness or accident striking themselves or a loved one) and how much time they take up. Explore if worries fill their thoughts during quiet or downtime, and explore more about their worries. You may use a screening instrument such as the Pediatric Symptom Checklist or the SCARED, both of which will indicate a likely problem with anxiety. While it is possible to have comorbid ADHD with an anxiety disorder, the anxiety disorder will likely worsen with stimulants and should be treated first. These are usually curable illnesses and you may find that remission of anxiety symptoms resolves the attentional problems.
Depression
Mood disorders are less common than anxiety disorders in youth, but far more prevalent than ADHD. And depression is usually marked by serious difficulty concentrating across settings (including for things that were previously very interesting). A sullen teenager who is deeply self-critical about school performance would benefit from exploration of associated changes in mood, interests, energy, appetite, sleep, and for feelings of worthlessness, guilt, and suicidal thoughts. The PHQ9A is a simple, free screening instrument that is reasonable to use with every sick visit (and well-check) with your adolescent patients, given the risks of undetected and untreated depression. If your patient presents complaining of poor school performance, always screen for depression. As with anxiety disorders, comorbid ADHD is possible, but it is always recommended to treat the mood disorder first and then to assess for residual ADHD symptoms once the mood disorder is in remission.
Substance abuse
Adolescence is a time of exploration, and drug and alcohol use is common. While attentional impairment will happen with intoxication, occasional or rare use should not lead to consistent impairment in school. But when parents are more worried than their children about a significant change in school performance, it is important to screen for substance abuse. A child with a secret substance use disorder will often present with behavioral changes and deteriorating school performance and might deny any drug or alcohol use to parents. Indeed, stimulants have some street value and some patients may be seeking a stimulant prescription to sell or trade for other drugs. Regular marijuana use may present with only deteriorating school performance and no irritability or other noticeable behavioral changes. Marijuana is seen as safe and even healthy by many teenagers (and even many parents), and some youth may be using it recreationally or to manage difficulties with sleep, anxiety, or mood symptoms.
But there is compelling evidence that marijuana use causes cognitive impairment, including difficulty with sustaining attention, short-term memory, and processing speed, for as long as 24 hours after use. If a teenager is using marijuana daily after school, it is certainly going to interfere, in a dose-dependent manner, with attention and cognitive function. Sustained heavy use can lead to permanent cognitive deficits. It can also trigger or worsen anxiety or mood symptoms (contrary to much popular opinion).
Gathering a thorough substance use history is essential when assessing a teenager for difficulties with focus or attention, especially when these are accompanied by change in behavior and school performance. Remember, it is critical to interview these children without their parents present to invite them to be forthcoming with you.
History
While true ADHD should have been present throughout childhood, it is possible that the symptoms have become noticeable only in adolescence. For patients with very high intelligence and lower levels of impulsivity and hyperactivity, they might easily have “flown under the radar” during their elementary and even middle school years. Their difficulties with attention and focus might become apparent only when the volume and difficulty of schoolwork both are great enough that their intelligence is not enough to get good grades. That is, their problems with executive function, prioritizing, shifting sets, and completing tasks in a timely way make it impossible to keep up good grades when the work gets harder.
Your history should reveal a long history of dreaminess or distractibility, a tendency to lose and forget things, and the other symptoms of inattention. Did they often seem to not be listening when they were younger? Forget to hand in homework? Leave chores unfinished? Leave messes behind everywhere they went? These will not be definitive, but they do reassure that symptoms may have been present for a long time, even if school performance was considered fine until the workload got too large. If such problems were not present before puberty, consider whether a subtle learning disability could be impairing them as they face more challenging academic subjects.
If you have ruled out anxiety, mood, and substance use concerns, and helped them to address a sleep deficit, then you can proceed. It is worthwhile to get Vanderbilt Assessments as you would for a younger child. If they meet criteria, discuss the risks and benefits of medication, executive skills coaching, and environmental adjustments (extra time for tests, a less stimulating environment) that can help them explore academic challenges without the discouragement that ADHD can bring.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
The context of our lives
Neuroscience expands our knowledge of relational and social worlds
Psychiatry may be emerging from the era of psychopharmacology and entering the era of the brain, but these reductionist, jingoistic labels do little justice to the need to acknowledge and incorporate the context of our lives into our theories and treatments. Yet psychiatrists who embrace context have much to celebrate in evolving neuroscience research.
One aptly named article – ’Families that fire together smile together’ – illustrates the fundamental connection between parent and child.1 In the functional MRIs (fMRIs) taken of these parent-child dyads (n = 76), the dyads with similar resting state connectomes also have similar day-to-day emotional states, as reflected in their diary entries. Their empathic states were identified in the multivoxel patterns in the fusiform face area of the brain.2 Another study of fMRIs and parent-child dyads (n = 93) found that the parental functional connectomes (fbc) predicted their children’s externalizing and internalizing problems. The maternal fbcs were correlated with the daughter-mother relationship, and to the daughter’s internalizing problems, suggesting a potential future focus on gendered relationships.3
The implications for psychotherapy are clear: These studies show that empathic connection between parent and child results in a better outcome for the child. Patient and psychotherapist can choose from a range of psychotherapeutic interventions that promote empathy, from providing behavioral tasks that support connection between parent and child to more in-depth family interventions. Family interventions that promote empathy include increasing the family’s understanding of the importance of empathic connection and providing a safe space to help establish empathic connection.
Studying prosocial behavior, Lukas Lengersdorff and colleagues found that fMRIs of male participants (n = 96) reflected stronger activity when they were acting on behalf of the other, rather than when acting for themselves.4 During this prosocial learning fMRI study, there was stronger engagement of the ventromedial prefrontal cortex (PFC) and higher connectivity between the ventromedial PFC and the right temporoparietal junction (rTPJ). Protecting others from harm appears to be associated with neural mechanisms that support self-relevant learning, but with the added recruitment of structures associated with the social brain. This study shows what we already know – that our brains are wired for social context. This research supports psychotherapeutic interventions aimed at creating interpersonal connection, not just at an intimate level, but also at the prosocial level, such as caring and helping others.
When social interactions are coded, the default mode network (DMN) shows increased activity. Participants (n = 11) in another study had heightened medial PFC–rTPJ connectivity, not only during rest that followed the experimental social encoding, but also during rest that followed a subsequent, nonsocial task.5 Engaging portions of the DMN during live social interactions when actively decoding the social environment, and later engaging these regions when relaxing after the social interaction, appears to facilitate social functioning. Our brains are wired to respond to context. This research underscores the positive impact of interventions such as group therapy and support groups, two underutilized modalities.
Neuroscience evaluation of our relationships provides depth to studies that fall under the medical paradigm of the gene/environment interaction. One of the most elegant in psychiatry is the Finnish study of a sample of offspring of mothers with schizophrenia who gave their children up for adoption.6 This sample of index offspring (n = 155) was compared blindly with matched controls (n = 186) of adopted/away offspring of parents without schizophrenia. The genetic effect manifested only as a psychiatric disorder in the presence of a disturbed family environment. We can now extrapolate certain possible mechanisms from the studies mentioned above: That the deficits lie in the activity or lack of activity in the DMN and associated areas, and in the generation of connectomes responsible for empathic connections.
Neuroscience expands our knowledge of our relational and social worlds, but can psychiatry make the case for inclusion of context in our conceptualization of psychiatric distress? From time to time, inroads are made, for example, the Global Assessment of Relational Functioning was incorporated into the DSM-IV-R and the Cultural Formulation Interview is in the DSM-5. However, without a sustained paradigm shift that places the gene/environment paradigm at the core of psychiatry, these efforts will rise and fall as the pioneers in these fields rise and fall.
A major barrier to moving the gene/environment paradigm more centrally in psychiatry is the prominence of individualism as an American ideal. As the neuroscience of context develops, we will be able to argue more robustly for a contextual approach to patient care.
A second barrier is the difficulty of teaching and learning about complexity. It is easy to learn how to use the DSM to make a diagnosis, to understand when and how to prescribe medications, but it is much more difficult to understand how to incorporate the complexity of life and the context within which we live, into our lexicon of psychiatric theories and treatments. As Tanya Luhrmann, PhD, points out in her study of the process of psychiatric training, residents are intimidated by the need to learn the many psychological theories and their practice; learning about medications is much simpler and takes much less time and effort.7
Nevertheless, context is embraced by several psychiatric subspecialties. Family psychiatrists recognize the power of relational dynamics in the family, and their role in shaping the individual. From understanding family communication patterns, to understanding how roles in the family get allocated, family psychiatry has well established tools for assessment and many evidence-based treatments that focus on changing relational dynamics. Social and community psychiatrists emphasize the role of race, poverty, and access, and support the assessment and treatment of the underprivileged. Cultural psychiatrists recognize that each culture has its own way of constructing identities and shaping our experiences, its own conceptualization of illness and specific idioms of distress. Cultural psychiatrists focus on sensitizing the general psychiatrist to these nuances. Child psychiatrists involve parents, and geriatric psychiatrists involve guardians. General psychiatrists understand context when, for example, understanding the role of trauma in the development of an individual, recognizing that its impact is contingent on the context within which the trauma occurs.
Neuroscience clarifies the neural pathways involved in the development of empathic and social behaviors. Our psychological theories and practice must reflect this advancement. We can teach the relevant neuroscience along with basic concepts such as child-parent relationships. We must assess an individual’s degree of fit within their family and community. Apart from asking relational questions, such as who in your world is important to you, we can use well recognized tools to help us bring context to the forefront. An easy tool is the three generational genogram, or an ecomap, which allows each individual to see where they sit in the context of their world.8 Cultural influences, societal, religious, and family influences can be drawn on the genogram, highlighting both formal and hidden family narratives. In addition, we can share how the brain works with our patients; the science of empathy and social behaviors shows us that our need for interpersonal connection is hardwired.
Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
References
1. Lee TH et al. Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads. Neuroimage. 2017 May 15;152:31-37. doi: 10.1016/j.neuroimage.2017.02.078.
2. Lee TH et al. Love flows downstream: Mothers’ and children’s neural representation similarity in perceiving distress of self and family. Soc Cogn Affect Neurosci. 2017 Dec 1;12(12):1916-27. doi: 10.1093/scan/nsx125.
3. Itahashi T et al. Functional connectomes linking child-parent relationships with psychological problems in adolescence. Neuroimage. 2020 Oct 1;219:117013. doi: 10.1016/j.neuroimage.2020.117013.
4. Lengersdorff LL et al. When implicit prosociality trumps selfishness: The neural valuation system underpins more optimal choices when learning to avoid harm to others than to oneself. J Neurosci. 2020 Sep 16;40(38):7286-99. doi: 10.1523/JNEUROSCI.0842-20.2020.
5. Meyer ML et al. Evidence that default network connectivity during rest consolidates social information. Cereb Cortex. 2019 May 1;29(5):1910-20. doi: 10.1093/cercor/bhy071.
6. Tienari P et al. The Finnish adoptive family study of schizophrenia. Implications for family research. Br J Psychiatry Suppl. 1994 Apr;(23):20-6.
7. Luhrmann, TM. Of two minds: The growing disorder in American psychiatry. New York, NY: Alfred A. Knopf, 2000.
8. Libbon R et al. Family skills for the resident toolbox: The 10-min. Genogram, Ecomap, and Prescribing Homework. Acad Psychiatry. 2019 Aug;43(4):435-439. doi: 10.1007/s40596-019-01054-6.
Neuroscience expands our knowledge of relational and social worlds
Neuroscience expands our knowledge of relational and social worlds
Psychiatry may be emerging from the era of psychopharmacology and entering the era of the brain, but these reductionist, jingoistic labels do little justice to the need to acknowledge and incorporate the context of our lives into our theories and treatments. Yet psychiatrists who embrace context have much to celebrate in evolving neuroscience research.
One aptly named article – ’Families that fire together smile together’ – illustrates the fundamental connection between parent and child.1 In the functional MRIs (fMRIs) taken of these parent-child dyads (n = 76), the dyads with similar resting state connectomes also have similar day-to-day emotional states, as reflected in their diary entries. Their empathic states were identified in the multivoxel patterns in the fusiform face area of the brain.2 Another study of fMRIs and parent-child dyads (n = 93) found that the parental functional connectomes (fbc) predicted their children’s externalizing and internalizing problems. The maternal fbcs were correlated with the daughter-mother relationship, and to the daughter’s internalizing problems, suggesting a potential future focus on gendered relationships.3
The implications for psychotherapy are clear: These studies show that empathic connection between parent and child results in a better outcome for the child. Patient and psychotherapist can choose from a range of psychotherapeutic interventions that promote empathy, from providing behavioral tasks that support connection between parent and child to more in-depth family interventions. Family interventions that promote empathy include increasing the family’s understanding of the importance of empathic connection and providing a safe space to help establish empathic connection.
Studying prosocial behavior, Lukas Lengersdorff and colleagues found that fMRIs of male participants (n = 96) reflected stronger activity when they were acting on behalf of the other, rather than when acting for themselves.4 During this prosocial learning fMRI study, there was stronger engagement of the ventromedial prefrontal cortex (PFC) and higher connectivity between the ventromedial PFC and the right temporoparietal junction (rTPJ). Protecting others from harm appears to be associated with neural mechanisms that support self-relevant learning, but with the added recruitment of structures associated with the social brain. This study shows what we already know – that our brains are wired for social context. This research supports psychotherapeutic interventions aimed at creating interpersonal connection, not just at an intimate level, but also at the prosocial level, such as caring and helping others.
When social interactions are coded, the default mode network (DMN) shows increased activity. Participants (n = 11) in another study had heightened medial PFC–rTPJ connectivity, not only during rest that followed the experimental social encoding, but also during rest that followed a subsequent, nonsocial task.5 Engaging portions of the DMN during live social interactions when actively decoding the social environment, and later engaging these regions when relaxing after the social interaction, appears to facilitate social functioning. Our brains are wired to respond to context. This research underscores the positive impact of interventions such as group therapy and support groups, two underutilized modalities.
Neuroscience evaluation of our relationships provides depth to studies that fall under the medical paradigm of the gene/environment interaction. One of the most elegant in psychiatry is the Finnish study of a sample of offspring of mothers with schizophrenia who gave their children up for adoption.6 This sample of index offspring (n = 155) was compared blindly with matched controls (n = 186) of adopted/away offspring of parents without schizophrenia. The genetic effect manifested only as a psychiatric disorder in the presence of a disturbed family environment. We can now extrapolate certain possible mechanisms from the studies mentioned above: That the deficits lie in the activity or lack of activity in the DMN and associated areas, and in the generation of connectomes responsible for empathic connections.
Neuroscience expands our knowledge of our relational and social worlds, but can psychiatry make the case for inclusion of context in our conceptualization of psychiatric distress? From time to time, inroads are made, for example, the Global Assessment of Relational Functioning was incorporated into the DSM-IV-R and the Cultural Formulation Interview is in the DSM-5. However, without a sustained paradigm shift that places the gene/environment paradigm at the core of psychiatry, these efforts will rise and fall as the pioneers in these fields rise and fall.
A major barrier to moving the gene/environment paradigm more centrally in psychiatry is the prominence of individualism as an American ideal. As the neuroscience of context develops, we will be able to argue more robustly for a contextual approach to patient care.
A second barrier is the difficulty of teaching and learning about complexity. It is easy to learn how to use the DSM to make a diagnosis, to understand when and how to prescribe medications, but it is much more difficult to understand how to incorporate the complexity of life and the context within which we live, into our lexicon of psychiatric theories and treatments. As Tanya Luhrmann, PhD, points out in her study of the process of psychiatric training, residents are intimidated by the need to learn the many psychological theories and their practice; learning about medications is much simpler and takes much less time and effort.7
Nevertheless, context is embraced by several psychiatric subspecialties. Family psychiatrists recognize the power of relational dynamics in the family, and their role in shaping the individual. From understanding family communication patterns, to understanding how roles in the family get allocated, family psychiatry has well established tools for assessment and many evidence-based treatments that focus on changing relational dynamics. Social and community psychiatrists emphasize the role of race, poverty, and access, and support the assessment and treatment of the underprivileged. Cultural psychiatrists recognize that each culture has its own way of constructing identities and shaping our experiences, its own conceptualization of illness and specific idioms of distress. Cultural psychiatrists focus on sensitizing the general psychiatrist to these nuances. Child psychiatrists involve parents, and geriatric psychiatrists involve guardians. General psychiatrists understand context when, for example, understanding the role of trauma in the development of an individual, recognizing that its impact is contingent on the context within which the trauma occurs.
Neuroscience clarifies the neural pathways involved in the development of empathic and social behaviors. Our psychological theories and practice must reflect this advancement. We can teach the relevant neuroscience along with basic concepts such as child-parent relationships. We must assess an individual’s degree of fit within their family and community. Apart from asking relational questions, such as who in your world is important to you, we can use well recognized tools to help us bring context to the forefront. An easy tool is the three generational genogram, or an ecomap, which allows each individual to see where they sit in the context of their world.8 Cultural influences, societal, religious, and family influences can be drawn on the genogram, highlighting both formal and hidden family narratives. In addition, we can share how the brain works with our patients; the science of empathy and social behaviors shows us that our need for interpersonal connection is hardwired.
Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
References
1. Lee TH et al. Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads. Neuroimage. 2017 May 15;152:31-37. doi: 10.1016/j.neuroimage.2017.02.078.
2. Lee TH et al. Love flows downstream: Mothers’ and children’s neural representation similarity in perceiving distress of self and family. Soc Cogn Affect Neurosci. 2017 Dec 1;12(12):1916-27. doi: 10.1093/scan/nsx125.
3. Itahashi T et al. Functional connectomes linking child-parent relationships with psychological problems in adolescence. Neuroimage. 2020 Oct 1;219:117013. doi: 10.1016/j.neuroimage.2020.117013.
4. Lengersdorff LL et al. When implicit prosociality trumps selfishness: The neural valuation system underpins more optimal choices when learning to avoid harm to others than to oneself. J Neurosci. 2020 Sep 16;40(38):7286-99. doi: 10.1523/JNEUROSCI.0842-20.2020.
5. Meyer ML et al. Evidence that default network connectivity during rest consolidates social information. Cereb Cortex. 2019 May 1;29(5):1910-20. doi: 10.1093/cercor/bhy071.
6. Tienari P et al. The Finnish adoptive family study of schizophrenia. Implications for family research. Br J Psychiatry Suppl. 1994 Apr;(23):20-6.
7. Luhrmann, TM. Of two minds: The growing disorder in American psychiatry. New York, NY: Alfred A. Knopf, 2000.
8. Libbon R et al. Family skills for the resident toolbox: The 10-min. Genogram, Ecomap, and Prescribing Homework. Acad Psychiatry. 2019 Aug;43(4):435-439. doi: 10.1007/s40596-019-01054-6.
Psychiatry may be emerging from the era of psychopharmacology and entering the era of the brain, but these reductionist, jingoistic labels do little justice to the need to acknowledge and incorporate the context of our lives into our theories and treatments. Yet psychiatrists who embrace context have much to celebrate in evolving neuroscience research.
One aptly named article – ’Families that fire together smile together’ – illustrates the fundamental connection between parent and child.1 In the functional MRIs (fMRIs) taken of these parent-child dyads (n = 76), the dyads with similar resting state connectomes also have similar day-to-day emotional states, as reflected in their diary entries. Their empathic states were identified in the multivoxel patterns in the fusiform face area of the brain.2 Another study of fMRIs and parent-child dyads (n = 93) found that the parental functional connectomes (fbc) predicted their children’s externalizing and internalizing problems. The maternal fbcs were correlated with the daughter-mother relationship, and to the daughter’s internalizing problems, suggesting a potential future focus on gendered relationships.3
The implications for psychotherapy are clear: These studies show that empathic connection between parent and child results in a better outcome for the child. Patient and psychotherapist can choose from a range of psychotherapeutic interventions that promote empathy, from providing behavioral tasks that support connection between parent and child to more in-depth family interventions. Family interventions that promote empathy include increasing the family’s understanding of the importance of empathic connection and providing a safe space to help establish empathic connection.
Studying prosocial behavior, Lukas Lengersdorff and colleagues found that fMRIs of male participants (n = 96) reflected stronger activity when they were acting on behalf of the other, rather than when acting for themselves.4 During this prosocial learning fMRI study, there was stronger engagement of the ventromedial prefrontal cortex (PFC) and higher connectivity between the ventromedial PFC and the right temporoparietal junction (rTPJ). Protecting others from harm appears to be associated with neural mechanisms that support self-relevant learning, but with the added recruitment of structures associated with the social brain. This study shows what we already know – that our brains are wired for social context. This research supports psychotherapeutic interventions aimed at creating interpersonal connection, not just at an intimate level, but also at the prosocial level, such as caring and helping others.
When social interactions are coded, the default mode network (DMN) shows increased activity. Participants (n = 11) in another study had heightened medial PFC–rTPJ connectivity, not only during rest that followed the experimental social encoding, but also during rest that followed a subsequent, nonsocial task.5 Engaging portions of the DMN during live social interactions when actively decoding the social environment, and later engaging these regions when relaxing after the social interaction, appears to facilitate social functioning. Our brains are wired to respond to context. This research underscores the positive impact of interventions such as group therapy and support groups, two underutilized modalities.
Neuroscience evaluation of our relationships provides depth to studies that fall under the medical paradigm of the gene/environment interaction. One of the most elegant in psychiatry is the Finnish study of a sample of offspring of mothers with schizophrenia who gave their children up for adoption.6 This sample of index offspring (n = 155) was compared blindly with matched controls (n = 186) of adopted/away offspring of parents without schizophrenia. The genetic effect manifested only as a psychiatric disorder in the presence of a disturbed family environment. We can now extrapolate certain possible mechanisms from the studies mentioned above: That the deficits lie in the activity or lack of activity in the DMN and associated areas, and in the generation of connectomes responsible for empathic connections.
Neuroscience expands our knowledge of our relational and social worlds, but can psychiatry make the case for inclusion of context in our conceptualization of psychiatric distress? From time to time, inroads are made, for example, the Global Assessment of Relational Functioning was incorporated into the DSM-IV-R and the Cultural Formulation Interview is in the DSM-5. However, without a sustained paradigm shift that places the gene/environment paradigm at the core of psychiatry, these efforts will rise and fall as the pioneers in these fields rise and fall.
A major barrier to moving the gene/environment paradigm more centrally in psychiatry is the prominence of individualism as an American ideal. As the neuroscience of context develops, we will be able to argue more robustly for a contextual approach to patient care.
A second barrier is the difficulty of teaching and learning about complexity. It is easy to learn how to use the DSM to make a diagnosis, to understand when and how to prescribe medications, but it is much more difficult to understand how to incorporate the complexity of life and the context within which we live, into our lexicon of psychiatric theories and treatments. As Tanya Luhrmann, PhD, points out in her study of the process of psychiatric training, residents are intimidated by the need to learn the many psychological theories and their practice; learning about medications is much simpler and takes much less time and effort.7
Nevertheless, context is embraced by several psychiatric subspecialties. Family psychiatrists recognize the power of relational dynamics in the family, and their role in shaping the individual. From understanding family communication patterns, to understanding how roles in the family get allocated, family psychiatry has well established tools for assessment and many evidence-based treatments that focus on changing relational dynamics. Social and community psychiatrists emphasize the role of race, poverty, and access, and support the assessment and treatment of the underprivileged. Cultural psychiatrists recognize that each culture has its own way of constructing identities and shaping our experiences, its own conceptualization of illness and specific idioms of distress. Cultural psychiatrists focus on sensitizing the general psychiatrist to these nuances. Child psychiatrists involve parents, and geriatric psychiatrists involve guardians. General psychiatrists understand context when, for example, understanding the role of trauma in the development of an individual, recognizing that its impact is contingent on the context within which the trauma occurs.
Neuroscience clarifies the neural pathways involved in the development of empathic and social behaviors. Our psychological theories and practice must reflect this advancement. We can teach the relevant neuroscience along with basic concepts such as child-parent relationships. We must assess an individual’s degree of fit within their family and community. Apart from asking relational questions, such as who in your world is important to you, we can use well recognized tools to help us bring context to the forefront. An easy tool is the three generational genogram, or an ecomap, which allows each individual to see where they sit in the context of their world.8 Cultural influences, societal, religious, and family influences can be drawn on the genogram, highlighting both formal and hidden family narratives. In addition, we can share how the brain works with our patients; the science of empathy and social behaviors shows us that our need for interpersonal connection is hardwired.
Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
References
1. Lee TH et al. Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads. Neuroimage. 2017 May 15;152:31-37. doi: 10.1016/j.neuroimage.2017.02.078.
2. Lee TH et al. Love flows downstream: Mothers’ and children’s neural representation similarity in perceiving distress of self and family. Soc Cogn Affect Neurosci. 2017 Dec 1;12(12):1916-27. doi: 10.1093/scan/nsx125.
3. Itahashi T et al. Functional connectomes linking child-parent relationships with psychological problems in adolescence. Neuroimage. 2020 Oct 1;219:117013. doi: 10.1016/j.neuroimage.2020.117013.
4. Lengersdorff LL et al. When implicit prosociality trumps selfishness: The neural valuation system underpins more optimal choices when learning to avoid harm to others than to oneself. J Neurosci. 2020 Sep 16;40(38):7286-99. doi: 10.1523/JNEUROSCI.0842-20.2020.
5. Meyer ML et al. Evidence that default network connectivity during rest consolidates social information. Cereb Cortex. 2019 May 1;29(5):1910-20. doi: 10.1093/cercor/bhy071.
6. Tienari P et al. The Finnish adoptive family study of schizophrenia. Implications for family research. Br J Psychiatry Suppl. 1994 Apr;(23):20-6.
7. Luhrmann, TM. Of two minds: The growing disorder in American psychiatry. New York, NY: Alfred A. Knopf, 2000.
8. Libbon R et al. Family skills for the resident toolbox: The 10-min. Genogram, Ecomap, and Prescribing Homework. Acad Psychiatry. 2019 Aug;43(4):435-439. doi: 10.1007/s40596-019-01054-6.
New law will awaken employers to health care’s ‘transparency gap’
It has become increasingly apparent that our health care system is suffering from a severe case of “transparency gap.” There is a lack of transparency at every level of care in the system. Whether it is the hidden rebate/fee kickbacks from drug manufacturers to pharmacy benefit managers (PBMs), or the variability in pricing of imaging and procedures based on site of care, the need for transparency has become acute. The health insurance sector seems to specialize in opaqueness. The vertical integration of the three largest insurance companies with the three largest PBMs seems to have trapped the flow of money and services in one big black box. It can be difficult to decide if this transparency gap is a case of missing information, misinformation, or a deliberate hiding of information … or maybe a combination of all three.
Recently, I testified before a Wisconsin State Senate committee about the consequences and potential harm to patients and physician offices caused by mandated “white bagging,” which refers to the process whereby provider-administered drugs are shipped to the provider by a specialty pharmacy, as opposed to the provider buying the drug and billing the insurance company. I was very surprised to hear the large employers testifying against our position.
As I listened to the employer groups, it was clear that their protestations were predominantly focused on hospital billing, where markups on the administered medications can be 500% and upward. It made sense that if a business has a “self-funded” health plan, where the employer pays for the cost of care of the employees, those very high markups on the hospital administered medications would eventually become unsustainable. In addition to paying for the care of employees, employers also pay the health insurance company/PBMs to administer the plan. It is obvious that self-funded businesses are being overwhelmed by all these rising costs. What is not so clear is how much information employers get from their plan administrators on their policies and pricing.
An Employee Benefit Research Institute (ERBI) study examined the difference in prices of health care procedures, labs, and imaging based on site of care. It clearly shows that physicians’ offices are the least expensive overall for infusion therapy, even when compared with home infusion in most cases.
Here is where the missing information and the white-bagging issue intersect. When insurance administrators tell employers that letting the provider “buy and bill” costs an outrageous amount, they fail to tell the employers that physicians’ office prices are comparable, or, in some cases, less than what the employer would pay with white bagging. In addition, the possible harm to patients and to the physicians’ practices are never mentioned to the employer. Here is a list of some of the problems associated with white bagging:
- Delays in patient care when dosages or treatment plans are modified during the patient visit.
- Significant waste of drugs when patients’ treatments change or appointments are rescheduled.
- Unnecessary administrative burden for both the patient and physician, including inventory nightmares.
We see the transparency gap again when formularies are created with higher-priced, branded drugs in place of lower-priced generics and alternatives. How can a PBM explain that a formulary that prefers a $10,000 prostate cancer drug but excludes the $400 generic of that drug actually saves money? If the employer doesn’t know about the generic, no explanation is needed.
When physician offices attempt to override some of these harmful policies, the PBM or insurance company often points the finger at the employer as the culprit responsible for the policy. Often, the employers have no idea of the ramifications of the contracts that they have signed. As health care costs continue to rise, it is important that employers are educated on how they can save money and improve patient care by directly contracting with independent physician practices.
In addition, the Consolidated Appropriation Act of 2020-21 (CAA) “seeks to enforce good value from providers and vendors, and forbids hidden contracting terms that disfavor employers and their employees.” This year and next, the employers will become responsible for transparency reporting and demonstrating cost effectiveness of therapies for their employees. In theory, this should uncover many of the hidden policies that favor only the health plans and not the patients or their employers. Many employers are unaware of the CAA, and vendors are in no hurry to inform them of it.
Not only will the CAA help to eliminate much of the transparency gap in the system, but it may encourage employers to work directly with independent physicians’ offices to provide more cost effective and transparent services for their patients. The Coalition of State Rheumatology Organizations is working on a framework to enable practicing rheumatologists to do exactly this.
In the meantime, we must continue educating employers on white bagging and other policies that harm both their patients and their “bottom line.” This education is just one of the steps needed to rid the health care system of the transparency gap that leads to higher prices and poorer care for all patients.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
It has become increasingly apparent that our health care system is suffering from a severe case of “transparency gap.” There is a lack of transparency at every level of care in the system. Whether it is the hidden rebate/fee kickbacks from drug manufacturers to pharmacy benefit managers (PBMs), or the variability in pricing of imaging and procedures based on site of care, the need for transparency has become acute. The health insurance sector seems to specialize in opaqueness. The vertical integration of the three largest insurance companies with the three largest PBMs seems to have trapped the flow of money and services in one big black box. It can be difficult to decide if this transparency gap is a case of missing information, misinformation, or a deliberate hiding of information … or maybe a combination of all three.
Recently, I testified before a Wisconsin State Senate committee about the consequences and potential harm to patients and physician offices caused by mandated “white bagging,” which refers to the process whereby provider-administered drugs are shipped to the provider by a specialty pharmacy, as opposed to the provider buying the drug and billing the insurance company. I was very surprised to hear the large employers testifying against our position.
As I listened to the employer groups, it was clear that their protestations were predominantly focused on hospital billing, where markups on the administered medications can be 500% and upward. It made sense that if a business has a “self-funded” health plan, where the employer pays for the cost of care of the employees, those very high markups on the hospital administered medications would eventually become unsustainable. In addition to paying for the care of employees, employers also pay the health insurance company/PBMs to administer the plan. It is obvious that self-funded businesses are being overwhelmed by all these rising costs. What is not so clear is how much information employers get from their plan administrators on their policies and pricing.
An Employee Benefit Research Institute (ERBI) study examined the difference in prices of health care procedures, labs, and imaging based on site of care. It clearly shows that physicians’ offices are the least expensive overall for infusion therapy, even when compared with home infusion in most cases.
Here is where the missing information and the white-bagging issue intersect. When insurance administrators tell employers that letting the provider “buy and bill” costs an outrageous amount, they fail to tell the employers that physicians’ office prices are comparable, or, in some cases, less than what the employer would pay with white bagging. In addition, the possible harm to patients and to the physicians’ practices are never mentioned to the employer. Here is a list of some of the problems associated with white bagging:
- Delays in patient care when dosages or treatment plans are modified during the patient visit.
- Significant waste of drugs when patients’ treatments change or appointments are rescheduled.
- Unnecessary administrative burden for both the patient and physician, including inventory nightmares.
We see the transparency gap again when formularies are created with higher-priced, branded drugs in place of lower-priced generics and alternatives. How can a PBM explain that a formulary that prefers a $10,000 prostate cancer drug but excludes the $400 generic of that drug actually saves money? If the employer doesn’t know about the generic, no explanation is needed.
When physician offices attempt to override some of these harmful policies, the PBM or insurance company often points the finger at the employer as the culprit responsible for the policy. Often, the employers have no idea of the ramifications of the contracts that they have signed. As health care costs continue to rise, it is important that employers are educated on how they can save money and improve patient care by directly contracting with independent physician practices.
In addition, the Consolidated Appropriation Act of 2020-21 (CAA) “seeks to enforce good value from providers and vendors, and forbids hidden contracting terms that disfavor employers and their employees.” This year and next, the employers will become responsible for transparency reporting and demonstrating cost effectiveness of therapies for their employees. In theory, this should uncover many of the hidden policies that favor only the health plans and not the patients or their employers. Many employers are unaware of the CAA, and vendors are in no hurry to inform them of it.
Not only will the CAA help to eliminate much of the transparency gap in the system, but it may encourage employers to work directly with independent physicians’ offices to provide more cost effective and transparent services for their patients. The Coalition of State Rheumatology Organizations is working on a framework to enable practicing rheumatologists to do exactly this.
In the meantime, we must continue educating employers on white bagging and other policies that harm both their patients and their “bottom line.” This education is just one of the steps needed to rid the health care system of the transparency gap that leads to higher prices and poorer care for all patients.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
It has become increasingly apparent that our health care system is suffering from a severe case of “transparency gap.” There is a lack of transparency at every level of care in the system. Whether it is the hidden rebate/fee kickbacks from drug manufacturers to pharmacy benefit managers (PBMs), or the variability in pricing of imaging and procedures based on site of care, the need for transparency has become acute. The health insurance sector seems to specialize in opaqueness. The vertical integration of the three largest insurance companies with the three largest PBMs seems to have trapped the flow of money and services in one big black box. It can be difficult to decide if this transparency gap is a case of missing information, misinformation, or a deliberate hiding of information … or maybe a combination of all three.
Recently, I testified before a Wisconsin State Senate committee about the consequences and potential harm to patients and physician offices caused by mandated “white bagging,” which refers to the process whereby provider-administered drugs are shipped to the provider by a specialty pharmacy, as opposed to the provider buying the drug and billing the insurance company. I was very surprised to hear the large employers testifying against our position.
As I listened to the employer groups, it was clear that their protestations were predominantly focused on hospital billing, where markups on the administered medications can be 500% and upward. It made sense that if a business has a “self-funded” health plan, where the employer pays for the cost of care of the employees, those very high markups on the hospital administered medications would eventually become unsustainable. In addition to paying for the care of employees, employers also pay the health insurance company/PBMs to administer the plan. It is obvious that self-funded businesses are being overwhelmed by all these rising costs. What is not so clear is how much information employers get from their plan administrators on their policies and pricing.
An Employee Benefit Research Institute (ERBI) study examined the difference in prices of health care procedures, labs, and imaging based on site of care. It clearly shows that physicians’ offices are the least expensive overall for infusion therapy, even when compared with home infusion in most cases.
Here is where the missing information and the white-bagging issue intersect. When insurance administrators tell employers that letting the provider “buy and bill” costs an outrageous amount, they fail to tell the employers that physicians’ office prices are comparable, or, in some cases, less than what the employer would pay with white bagging. In addition, the possible harm to patients and to the physicians’ practices are never mentioned to the employer. Here is a list of some of the problems associated with white bagging:
- Delays in patient care when dosages or treatment plans are modified during the patient visit.
- Significant waste of drugs when patients’ treatments change or appointments are rescheduled.
- Unnecessary administrative burden for both the patient and physician, including inventory nightmares.
We see the transparency gap again when formularies are created with higher-priced, branded drugs in place of lower-priced generics and alternatives. How can a PBM explain that a formulary that prefers a $10,000 prostate cancer drug but excludes the $400 generic of that drug actually saves money? If the employer doesn’t know about the generic, no explanation is needed.
When physician offices attempt to override some of these harmful policies, the PBM or insurance company often points the finger at the employer as the culprit responsible for the policy. Often, the employers have no idea of the ramifications of the contracts that they have signed. As health care costs continue to rise, it is important that employers are educated on how they can save money and improve patient care by directly contracting with independent physician practices.
In addition, the Consolidated Appropriation Act of 2020-21 (CAA) “seeks to enforce good value from providers and vendors, and forbids hidden contracting terms that disfavor employers and their employees.” This year and next, the employers will become responsible for transparency reporting and demonstrating cost effectiveness of therapies for their employees. In theory, this should uncover many of the hidden policies that favor only the health plans and not the patients or their employers. Many employers are unaware of the CAA, and vendors are in no hurry to inform them of it.
Not only will the CAA help to eliminate much of the transparency gap in the system, but it may encourage employers to work directly with independent physicians’ offices to provide more cost effective and transparent services for their patients. The Coalition of State Rheumatology Organizations is working on a framework to enable practicing rheumatologists to do exactly this.
In the meantime, we must continue educating employers on white bagging and other policies that harm both their patients and their “bottom line.” This education is just one of the steps needed to rid the health care system of the transparency gap that leads to higher prices and poorer care for all patients.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
Selling your practice
My previous column on practice valuation prompted a number of questions on the mechanics of selling a private practice. As usual, I cannot hope to cover this complex topic comprehensively in only 750 words, but here are the basics.
A generation ago, the sale of a medical practice was much like the sale of any other business: A retiring physician would sell his or her practice to a young doctor and the practice would continue on as before. Occasionally, that still happens, but changes in the business of medicine – most significantly the growth of managed care – have had a big impact on the way medical practices are bought and sold.
For one thing, there are far fewer solo practitioners these days, and polls indicate that most young physicians intend to continue that trend. .
For another, because the rules governing such sales have become so numbingly complex, the services of expert (and expensive) third parties are essential.
While these issues may complicate matters, there is still a market for the sale of medical practices. However, you must do everything possible to ensure you identify the best possible buyer and structure the best deal.
The first hurdle is the accurate valuation of your practice, which was covered in some detail in my last column. Briefly, for the protection of both parties, it is important that the appraisal be done by an experienced and neutral financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation be supplied to support the conclusions reached.
Keep in mind that the valuation will not necessarily equal the purchase price; other factors may need to be considered before a final price can be agreed upon. Keep in mind, too, that there may be legal constraints on the purchase price. For example, if the buyer is a nonprofit corporation such as a hospital or HMO, by law it cannot pay in excess of fair market value for the practice – which may rule out any valuation of “good will.” In some states, the purchase of private practices by hospitals is prohibited altogether – so you might need to consider a long-term lease rather than a sale.
Once a value has been agreed upon, you must consider how the transaction will be structured. The most popular structures include purchase of assets, purchase of corporate stock, and merger.
Many buyers prefer to purchase assets, because it allows them to pick and choose only those items that have value to them. This can leave you with a bunch of “odd lot” assets to dispose of. But depending on the circumstances, an asset sale may still be to your advantage.
Sellers typically prefer to sell stock, because it allows them to sell their entire practice, which is often worth more than the sum of its parts, and often provides tax advantages.
The third option, merger, continues to grow in popularity and is a column subject in itself, and I will address it separately next month.
Tax issues must always be considered. Most private practices are corporations, and the sale of corporate stock will result in a long-term capital gain that will be taxed – currently at 15%-20%. As the saying goes, it’s not what you earn, it’s what you keep. So it may benefit you to accept a slightly lower price if the sale can be structured to provide significantly lower tax treatment. However, any gain that does not qualify as a long-term capital gain will be taxed as regular income – currently in the 32%-37% percent range – plus a Social Security tax of about 15%.
Payment in installments is a popular way to defer taxes, since they are incurred on each installment as it is paid; but such payments may be mistaken by the IRS for payments for referrals, which is illegal. And there is always the problem of making certain all payments are eventually made.
You may wish to continue working at the practice as an employee for an agreed-upon period of time, and this is often to the buyer’s advantage as well. Transitioning to new ownership in stages often maximizes the value of the business by improving patient retention, and allows patients to become accustomed to the transition. However, care must be taken, with the aid of good legal advice, to structure such an arrangement in a way that minimizes concerns of fraud and abuse.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
My previous column on practice valuation prompted a number of questions on the mechanics of selling a private practice. As usual, I cannot hope to cover this complex topic comprehensively in only 750 words, but here are the basics.
A generation ago, the sale of a medical practice was much like the sale of any other business: A retiring physician would sell his or her practice to a young doctor and the practice would continue on as before. Occasionally, that still happens, but changes in the business of medicine – most significantly the growth of managed care – have had a big impact on the way medical practices are bought and sold.
For one thing, there are far fewer solo practitioners these days, and polls indicate that most young physicians intend to continue that trend. .
For another, because the rules governing such sales have become so numbingly complex, the services of expert (and expensive) third parties are essential.
While these issues may complicate matters, there is still a market for the sale of medical practices. However, you must do everything possible to ensure you identify the best possible buyer and structure the best deal.
The first hurdle is the accurate valuation of your practice, which was covered in some detail in my last column. Briefly, for the protection of both parties, it is important that the appraisal be done by an experienced and neutral financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation be supplied to support the conclusions reached.
Keep in mind that the valuation will not necessarily equal the purchase price; other factors may need to be considered before a final price can be agreed upon. Keep in mind, too, that there may be legal constraints on the purchase price. For example, if the buyer is a nonprofit corporation such as a hospital or HMO, by law it cannot pay in excess of fair market value for the practice – which may rule out any valuation of “good will.” In some states, the purchase of private practices by hospitals is prohibited altogether – so you might need to consider a long-term lease rather than a sale.
Once a value has been agreed upon, you must consider how the transaction will be structured. The most popular structures include purchase of assets, purchase of corporate stock, and merger.
Many buyers prefer to purchase assets, because it allows them to pick and choose only those items that have value to them. This can leave you with a bunch of “odd lot” assets to dispose of. But depending on the circumstances, an asset sale may still be to your advantage.
Sellers typically prefer to sell stock, because it allows them to sell their entire practice, which is often worth more than the sum of its parts, and often provides tax advantages.
The third option, merger, continues to grow in popularity and is a column subject in itself, and I will address it separately next month.
Tax issues must always be considered. Most private practices are corporations, and the sale of corporate stock will result in a long-term capital gain that will be taxed – currently at 15%-20%. As the saying goes, it’s not what you earn, it’s what you keep. So it may benefit you to accept a slightly lower price if the sale can be structured to provide significantly lower tax treatment. However, any gain that does not qualify as a long-term capital gain will be taxed as regular income – currently in the 32%-37% percent range – plus a Social Security tax of about 15%.
Payment in installments is a popular way to defer taxes, since they are incurred on each installment as it is paid; but such payments may be mistaken by the IRS for payments for referrals, which is illegal. And there is always the problem of making certain all payments are eventually made.
You may wish to continue working at the practice as an employee for an agreed-upon period of time, and this is often to the buyer’s advantage as well. Transitioning to new ownership in stages often maximizes the value of the business by improving patient retention, and allows patients to become accustomed to the transition. However, care must be taken, with the aid of good legal advice, to structure such an arrangement in a way that minimizes concerns of fraud and abuse.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
My previous column on practice valuation prompted a number of questions on the mechanics of selling a private practice. As usual, I cannot hope to cover this complex topic comprehensively in only 750 words, but here are the basics.
A generation ago, the sale of a medical practice was much like the sale of any other business: A retiring physician would sell his or her practice to a young doctor and the practice would continue on as before. Occasionally, that still happens, but changes in the business of medicine – most significantly the growth of managed care – have had a big impact on the way medical practices are bought and sold.
For one thing, there are far fewer solo practitioners these days, and polls indicate that most young physicians intend to continue that trend. .
For another, because the rules governing such sales have become so numbingly complex, the services of expert (and expensive) third parties are essential.
While these issues may complicate matters, there is still a market for the sale of medical practices. However, you must do everything possible to ensure you identify the best possible buyer and structure the best deal.
The first hurdle is the accurate valuation of your practice, which was covered in some detail in my last column. Briefly, for the protection of both parties, it is important that the appraisal be done by an experienced and neutral financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation be supplied to support the conclusions reached.
Keep in mind that the valuation will not necessarily equal the purchase price; other factors may need to be considered before a final price can be agreed upon. Keep in mind, too, that there may be legal constraints on the purchase price. For example, if the buyer is a nonprofit corporation such as a hospital or HMO, by law it cannot pay in excess of fair market value for the practice – which may rule out any valuation of “good will.” In some states, the purchase of private practices by hospitals is prohibited altogether – so you might need to consider a long-term lease rather than a sale.
Once a value has been agreed upon, you must consider how the transaction will be structured. The most popular structures include purchase of assets, purchase of corporate stock, and merger.
Many buyers prefer to purchase assets, because it allows them to pick and choose only those items that have value to them. This can leave you with a bunch of “odd lot” assets to dispose of. But depending on the circumstances, an asset sale may still be to your advantage.
Sellers typically prefer to sell stock, because it allows them to sell their entire practice, which is often worth more than the sum of its parts, and often provides tax advantages.
The third option, merger, continues to grow in popularity and is a column subject in itself, and I will address it separately next month.
Tax issues must always be considered. Most private practices are corporations, and the sale of corporate stock will result in a long-term capital gain that will be taxed – currently at 15%-20%. As the saying goes, it’s not what you earn, it’s what you keep. So it may benefit you to accept a slightly lower price if the sale can be structured to provide significantly lower tax treatment. However, any gain that does not qualify as a long-term capital gain will be taxed as regular income – currently in the 32%-37% percent range – plus a Social Security tax of about 15%.
Payment in installments is a popular way to defer taxes, since they are incurred on each installment as it is paid; but such payments may be mistaken by the IRS for payments for referrals, which is illegal. And there is always the problem of making certain all payments are eventually made.
You may wish to continue working at the practice as an employee for an agreed-upon period of time, and this is often to the buyer’s advantage as well. Transitioning to new ownership in stages often maximizes the value of the business by improving patient retention, and allows patients to become accustomed to the transition. However, care must be taken, with the aid of good legal advice, to structure such an arrangement in a way that minimizes concerns of fraud and abuse.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Appropriate cancer screening for women with dense breasts
We have been interested in the quiz series focused on breast cancer screening for women with dense breasts presented in
The concerns with breast cancer in particular
Breast cancer is not cervical cancer. It isn’t one disease. It is a multitude of diseases that happen to show up in the breast. Some are relatively slow-growing—the kinds of cancers that lend themselves to screening and to early intervention. But other cancers are rapidly-growing; they show up no matter how often or what modality we use for screening. Our goal should be to find an approach to screening that can diagnose breast cancer at a stage where we can intervene and positively impact breast cancer specific and overall mortality.
Screening guidelines vary
The variety of screening guidelines published by different professional organizations reflect differing assumptions and sets of values related to the early diagnosis and treatment of breast cancer. (For a comprehensive table of current screening guidelines, see https://www.cdc.gov/cancer/breast/pdf/breast-cancer-screening-guidelines-508.pdf.)
ACOG’s approach—to offer screening at age 40 but to begin by at least age 50 and, through shared decision making with the patient, screen every 1 or 2 years—is focused on capturing as many cases as we can identify, while minimizing the harms of false-positives.1 The perspective of the US Preventive Services Task Force (USPSTF) recommendations (to screen every 2 years beginning at age 50) is at the population level, a cost-effective approach that will have the greatest benefit while minimizing harms in the population at large.2 The American Society of Breast Surgeons recommends screening to begin by age 40.3 Like the breast surgeons, radiologists dedicated to breast imaging are focused on an individual rather than a population level. They strive to identify each and every instance of possible cancer, and therefore recommend annual screening beginning at age 40.4 However, with more aggressive screening in average-risk women many cases of ductal carcinoma in situ (DCIS) are identified—a lesion that, if not detected, may not impact the woman’s health during her lifetime—representing what some might call “overdiagnosis.” Yet there may be some instances in which the DCIS might affect an individual woman’s health. Unfortunately, we can’t prospectively distinguish between the first and the second types of cases.
We follow American College of Obstetricians and Gynecologists and US Preventive Services Task Force guidelines in discussing screening (both its hazards and benefits) with our average-risk patients beginning at age 40. We talk about risk factors for breast cancer, including breast density, but let patients know that no specific additional imaging is advised, and that density is more common in younger women (one consideration in earlier screening) and is quite common in general. Although we do not send follow-up letters to patients with dense breasts, we do educate our staff so that they can respond appropriately should patients call with questions.
Of course, we all bring to the table values that will impact the decisions that we make for ourselves and for our patients. What an ObGyn might suggest may differ from what a radiologist might suggest. Although we follow recommendations made by the radiologist at screening, an ObGyn wants to take care of the whole human being. We are concerned with bones, heart, everything about the patient, so we approach a patient in a different way. These priorities are reflected in the current varying breast cancer screening guidelines.
Continue to: Research on breast cancer screening varies by design...
Research on breast cancer screening varies by design
There has not been a randomized clinical trial conducted on screening mammography since the days of the analog mammogram. The research that has been conducted is difficult to compare due to variations in screening ages and intervals, technology sensitivity, and patient adherence with recommended screening. Treatments for breast cancer also have changed dramatically over time, so the findings of older studies may no longer be relevant to current breast cancer screening. The kind of analysis that needs to be done is an interrupted time series, where you can look at the trajectory of breast cancer survival and whether screening mammography shifts that survival in any way.
One specific study from Australia measured the impact of newer available breast cancer treatments, including tamoxifen for women with receptor-positive tumors and newer chemotherapy strategies.5 The authors analyzed screening mammography trends in one large province where women aged 50 to 69 were offered biennial screening. Trends from the 1990s showed that more women were being screened over time. Simultaneously, however, advances in therapy were entering clinical practice. The researchers pointed to a substantial decline in mortality from breast cancer from the early 1980s until 2013. But their conclusion was that none of the decline in mortality for breast cancer could be attributed to screening mammography when they looked at time trends; from their perspective all of the important decline in breast cancer mortality resulted from better treatment. They concluded that government programs should not support screening mammography.5
That is a recommendation that we do not support. However, we do recognize the conundrum that mammography is less sensitive among those who have dense breasts. In order to have congruent professional guidelines, we support research funding to determine which types, starting ages, and intervals of screening would be best in various patient populations. The USPSTF cites data from studies performed in the 1980s based on outdated technology; more recent (and relevant) randomized clinical trials have not been performed, and yet this information is critical to provide sufficient evidence to develop appropriate guidelines.
Our recommendations for gathering new data
The kind of data we would find most valuable would assess how different screening strategies impact overall mortality and breast cancer-specific mortality. It would require decades of follow-up—which of course means that screening technology will change over that time. A surrogate for evaluating overall survival is to look at interval cancers, which are all breast cancers diagnosed following negative mammograms and prior to the next screening. These cancers may or may not be biologically active, again focusing us on the need to look at overall survival of the patient. In addition, reducing breast cancer mortality may not reduce overall mortality, because the treatment for breast cancer may cause heart disease, or osteoporosis, or something else that impacts overall survival. These are important considerations for women and physicians who are making choices on treatment. What matters to a patient are 2 overlapping questions:
- Do I have a life-threatening condition or do I not?
- Has screening identified a condition that might lead to treatment that’s unnecessary?
The problem is that with breast cancer we can’t tell the difference. We do not understand the biological potential of a lesion when we evaluate an image on MRI, or computed tomography (CT), or mammography.
A re-look at presented data
A trial conducted by Bakker and colleagues6 was discussed by the authors of the DenseBreast-info.org quiz in which they recommended breast MRI for all women with extremely dense breasts (but no other risk factors for breast cancer) detected on screening mammograms.7 The Bakker study was large and conducted in the Netherlands. The primary outcome of the trial was to compare the incidence of interval breast cancers of women aged 50 to 75 randomly assigned to MRI versus those assigned to continued screening mammography every 2 years. Importantly, among the more than 8,000 women who were assigned to MRI, 59%, or fewer than two-thirds, chose to actually undergo MRI.
Among women randomized to MRI, 20 interval cancers were found—4 were diagnosed in those who actually had MRIs, and 16 were diagnosed among women who were randomized to MRI but didn’t undergo the study. Among women assigned to screening mammography only, 161 interval cancers were diagnosed among more than 32,000 women screened. The primary outcome findings were 2.5 interval cancers per 1,000 screenings among women randomly assigned to MRI, and 5 interval cancers per 1,000 screenings among those randomly assigned to mammography only.6
Because the trial included women aged 50 and older, we can’t apply these results to younger women, who often undergo screening mammography in the United States. In addition, the majority of the population in the Netherlands are of Western European ethnicity, a less-diverse population of women than in the United States. Furthermore, among the tumors that were detected in the MRI group, a larger proportion were DCIS, early-stage tumors, well differentiated, and hormone receptor-positive. This observation supports that many of the MRI-detected tumors were cases of overdiagnosis, or the detection of tumors destined not to cause clinical problems for the patient during her lifetime, or for which earlier diagnosis would impact survival.
We also know that treatment of these small ER-positive tumors carries risks for patients, as we may treat them by depriving a patient of estrogen for the rest of her life, with potential consequences of sexual dysfunction, osteoporosis, and perhaps cardiovascular disease depending on her age at the time of that diagnosis. Weighing the risks and benefits of not only treatment but also use of more sensitive screening techniques such as MRI is extremely important. Although Bakker and colleagues’ study results are interesting, we do not feel they support routinely recommending MRI for women found to have extremely dense breasts with mammography.
Overdiagnosis: A difficult concept
One reason overdiagnosis is so challenging to understand is that it can’t be directly measured, which makes comprehending it that much more problematic for clinicians and our patients.
One way to help grasp the overall issue is to compare screening mammography with cervical and colon cancer screening.
We are well aware that cervical cancer screening has reduced the incidence of mortality from invasive cervical cancer.8 We can argue very validly that the biggest success in any cancer screening program in history and globally has been cervical cancer screening. Our specialty, in particular, should feel proud about this. Screening colonoscopy also has repeatedly been found to reduce colon cancer mortality.9 For breast cancer, decades of media messaging have emphasized the benefits of screening mammograms; however, in contrast with cervical cancer screening and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic or advanced disease. Danish authors pointed out in 2017 that screening mammography has not achieved the hoped for or the promised reduction in breast cancer mortality.10
A report published in the March 2022, issue of Annals of Internal Medicine used modeling techniques to estimate the incidence of overdiagnosis and concluded that, among women aged 50-74 years receiving biennial screening mammograms (consistent with USPSTF recommendations), more than 15% of screen-detected breast cancers would represent cases of overdiagnosis. Of note, the study authors found that, among screen-detected cancers, the proportion representing overdiagnosis among women in their 60s (16.7%) and early 70s (23.6%) was higher than among women in their 50s-60s (11.5%-11.6%).11
The former Chief Medical and Scientific Officer for the American Cancer Society Otis Brawley, MD, has stated that, at the same time that breast cancer screening should not be abandoned, “We must acknowledge that overdiagnosis is common. The benefits of screening have been overstated, and some patients considered as ‘cured’ from breast cancer have, in fact, been harmed by unneeded treatment.”12
“Everybody loves early detection,” said Donald Berry, PhD, from MD Anderson Cancer Center, “but it comes with harms.” He points out that mortality rates have improved for breast cancer, but he attributes it to improved treatment. “The harms [of screening] we know, but the benefits of screening are very uncertain.”13
The importance of health equity is receiving more attention. When examining equity according to breast cancer mortality, ethnic minority populations have worse cancer survival outcomes than White women; the mortality rate is 40% higher among Black women than among White women.1 Lower survival rates are also noted among lower socioeconomic groups and among women who live in rural areas. Lower survival rates among ethnic minority women are also noted for cervical and colorectal cancers.2
In the past, these disparities in mortality were attributed to the historically lower breast cancer screening rates among Black women compared with White women. However, decades of efforts to increase mammography rates have effectively addressed much of the racial/ethnic gap in screening rates.1 In fact, a 2021 study showed Black and Hispanic women to have 6% to 10% higher rates of breast, cervical, and colorectal cancer screening than White women according to US Preventive Services Task Force guidelines.2 The study authors point out that other national data have demonstrated similar results and conclude that “higher cancer mortality among racial/ethnic minority groups will not be reduced solely by increasing rates of cancer screening. Although preventive screenings and timely diagnosis are important elements of prognosis, they are just 2 elements of many along the cancer care continuum that need to be addressed to eliminate disparities in cancer mortality.”
Unfortunately, the randomized trials that have been conducted on mammography have been conducted overwhelmingly in White populations. National registry studies from the Netherlands and Sweden are not representative patient populations for the United States. Recently, the US government proposed an ambitious plan to cut cancer mortality rates and has promised vast amounts of research funding to achieve that goal.3 Hopefully, this funding will support studies which enroll diverse patient populations. We hope to gain knowledge on what elements along the cancer care continuum can be addressed to better reduce or eliminate cancer mortality inequities.
References
1. National Cancer Institute. SEER Explorer. https://seer.cancer.gov/explorer/. Accessed February 9, 2022.
2. Benavidez GA, Zgodic A, Zahnd WE, Eberth JM. Disparities in Meeting USPSTF Breast, Cervical, and Colorectal Cancer Screening Guidelines Among Women in the United States. Prev Chronic Dis. 2021;18:200315. doi: http://dx.doi.org/10.5888/pcd18.200315.
3. Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
Continue to: Limitations of breast MRI...
Limitations of breast MRI
Overall, MRI is a diagnostic and monitoring test. It is costlier than mammography, and because it is not recommended in guidelines as a screening modality for most women, it is not typically covered by insurance. Abbreviated (rapid) MRI is a non-standardized imaging strategy being used at a few health centers. It has a shorter protocol overall than MRI, so it takes less time than current MRI and is less expensive, but there are few data on sensitivity and specificity. It is yet to be determined which populations could benefit from this newer technology.
As mentioned, 41% of women in the Bakker et al trial who were randomly assigned to breast MRI chose not to proceed with that exam even though it would have been at no cost to them.6 Anecdotally, some patients who have undergone MRI say they would forgo it a second time as a screening modality because it was a very unpleasant, stressful experience. It’s not a perfect test, although it is more sensitive than mammography.
Other options for following up dense-breast screening. Besides MRI and abbreviated MRI, the following modalities can be used to evaluate women found to have dense breasts with screening mammograms: CT mammography with contrast, molecular breast imaging, and ultrasonography.
Screening and treatment advances
3D mammography. In the US, the great majority of screening mammography now is performed with tomosynthesis, or what our patients sometimes call 3D mammography. In fact, it is approaching standard of care. Women whose screening mammography includes tomosynthesis are less likely to experience a so-called callback for additional imaging with diagnostic mammography or breast ultrasonography.14
Liquid biopsy. A potential major advancement for making decisions about when to treat cancers in general involves determining the biological behavior of a tumor, based on analysis of either circulating tumor DNA or proteins in the blood. As more experience with this new technology accumulates, the role of liquid biopsies for breast cancer will expand.15 Liquid biopsies for screening remain investigational for now, but they hold tremendous potential.
Noninvasive proteomics. With the development of noninvasive proteomic biomarkers obtained from blood, saliva, or nipple aspiration fluid, there exists the possibility of not just evaluating an image of a tumor seen on a mammogram, but actually studying the biological characteristics of that lesion.16 The cost of this technology is far less in terms of resources than MRI or molecular-based imaging, and actually reveals the flaws with using image-based screening. With proteomics, we can tell whether or not a lump is generating proteins that are going to make that disease biologically meaningful, and treatment decisions can be based on that information. This idea has the potential to disrupt our current breast cancer screening paradigm.
Advocacy’s role in mandating legislation
Many advocacy groups lobby on Capitol Hill for legislation related to health care, but we don’t feel that is the best way to make scientific decisions, and it’s not the way to do medicine. Passionate people, who truly believe that their outcome would have been different had something else been done, have every right to advocate, and should. However, without longer-term data focusing on breast cancer and overall mortality, rather than surrogate outcomes like interval cancers, it is not clear that routinely recommending supplemental MRI will improve survival for women with extremely dense breasts. Unfortunately, overall, earlier diagnosis of highly aggressive breast cancer tumors does not result in better outcomes for patients. ●
- American College of Obstetricians and Gynecologists. Practice Bulletin number 179: breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130: e1-e16. doi: 10.1097/AOG.0000000000002158.
- Sui AL, U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:279-296. doi: 10.7326/M15-2886.
- The American Society of Breast Surgeons. Position statement on screening mammography. https://www.breastsurgeons.org/docs /statements/Position-Statement-on-ScreeningMammography.pdf. Accessed February 15, 2022.
- Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average-risk: update from the ACR and Society of Breast Imaging. J Am College Radiol. 2021;18:1280-1288.
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020;3:e208249.
- Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102. doi: 10.1056/NEJMoa1903986.
- Seitzman R, Berg W. Average-risk women with dense breasts—what breast screening is appropriate? OBG Manag. 2021;33:18-19. doi: 10.12788/obgm.0155.
- Gopalani SV, Janitz AE, Campbell JE. Cervical cancer incidence and mortality among non-hispanic African American and White women, United States, 1999-2015. J Natl Med Assoc. 2020;112:632-638. doi: 10.1016 /j.jnma.2020.06.007.
- Niikura R, Hirata Y, Suzuki N, et al. Colonoscopy reduces colorectal cancer mortality: a multicenter, long-term, colonoscopy-based cohort study. PLoS One. 2017;12:e0185294.
- Jørgensen KJ, Gøtzsche PC, Kalager M, et al. Breast cancer screening in Denmark. Ann Intern Med. 2017;167:524. doi: 10.7326/L17-0270.
- Ryser MD, Lange J, Inoue IL, et al. Estimation of breast cancer overdiagnosis in a U.S. breast screening cohort. Ann Intern Med. 2022 March 1. doi: 10.7326/M21-3577.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis. Ann Intern Med. 2017;166:364-365. doi:10.7326/M16-2850.
- Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
- Conant EF, Barlow WE, Herschorn SD, et al. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-642. doi: 10.1001 /jamaoncol.2018.7078.
- Tay TK, Tan PH. Liquid biopsy in breast cancer: a focused review. Arch Pathol Lab Med. 2021;145: 678-686. doi: 10.5858/arpa.2019-0559-RA.
- Debald M, Wolgarten M, Walgenbach-Brunagel G, et al. Non-invasive proteomics—thinking about personalized breast cancer screening and treatment. EPMA J. 2010;1:413-420. doi: 10.1007 /s13167-010-0039-9.
Barbara Levy, MD
Dr. Levy is Clinical Professor, Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences and Principal, The Levy Group LLC, La Jolla, California. She is a member of the OBG Management Board of Editors.
Andrew M. Kaunitz, MD, NCMP
Dr. Kaunitz is Tenured Professor and Associate Chair, Department of Obstetrics and Gynecology, University of Florida College of Medicine– Jacksonville; and Medical Director and Director of Menopause and Gynecologic Ultrasound Services, University of Florida Health Women’s Specialist Services–Emerson, Jacksonville. He serves on the OBG Management Board of Editors.
Dr. Levy reports being a consultant to Hologic. Dr. Kaunitz reports no financial relationships relevant to this article.
Barbara Levy, MD
Dr. Levy is Clinical Professor, Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences and Principal, The Levy Group LLC, La Jolla, California. She is a member of the OBG Management Board of Editors.
Andrew M. Kaunitz, MD, NCMP
Dr. Kaunitz is Tenured Professor and Associate Chair, Department of Obstetrics and Gynecology, University of Florida College of Medicine– Jacksonville; and Medical Director and Director of Menopause and Gynecologic Ultrasound Services, University of Florida Health Women’s Specialist Services–Emerson, Jacksonville. He serves on the OBG Management Board of Editors.
Dr. Levy reports being a consultant to Hologic. Dr. Kaunitz reports no financial relationships relevant to this article.
Barbara Levy, MD
Dr. Levy is Clinical Professor, Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences and Principal, The Levy Group LLC, La Jolla, California. She is a member of the OBG Management Board of Editors.
Andrew M. Kaunitz, MD, NCMP
Dr. Kaunitz is Tenured Professor and Associate Chair, Department of Obstetrics and Gynecology, University of Florida College of Medicine– Jacksonville; and Medical Director and Director of Menopause and Gynecologic Ultrasound Services, University of Florida Health Women’s Specialist Services–Emerson, Jacksonville. He serves on the OBG Management Board of Editors.
Dr. Levy reports being a consultant to Hologic. Dr. Kaunitz reports no financial relationships relevant to this article.
We have been interested in the quiz series focused on breast cancer screening for women with dense breasts presented in
The concerns with breast cancer in particular
Breast cancer is not cervical cancer. It isn’t one disease. It is a multitude of diseases that happen to show up in the breast. Some are relatively slow-growing—the kinds of cancers that lend themselves to screening and to early intervention. But other cancers are rapidly-growing; they show up no matter how often or what modality we use for screening. Our goal should be to find an approach to screening that can diagnose breast cancer at a stage where we can intervene and positively impact breast cancer specific and overall mortality.
Screening guidelines vary
The variety of screening guidelines published by different professional organizations reflect differing assumptions and sets of values related to the early diagnosis and treatment of breast cancer. (For a comprehensive table of current screening guidelines, see https://www.cdc.gov/cancer/breast/pdf/breast-cancer-screening-guidelines-508.pdf.)
ACOG’s approach—to offer screening at age 40 but to begin by at least age 50 and, through shared decision making with the patient, screen every 1 or 2 years—is focused on capturing as many cases as we can identify, while minimizing the harms of false-positives.1 The perspective of the US Preventive Services Task Force (USPSTF) recommendations (to screen every 2 years beginning at age 50) is at the population level, a cost-effective approach that will have the greatest benefit while minimizing harms in the population at large.2 The American Society of Breast Surgeons recommends screening to begin by age 40.3 Like the breast surgeons, radiologists dedicated to breast imaging are focused on an individual rather than a population level. They strive to identify each and every instance of possible cancer, and therefore recommend annual screening beginning at age 40.4 However, with more aggressive screening in average-risk women many cases of ductal carcinoma in situ (DCIS) are identified—a lesion that, if not detected, may not impact the woman’s health during her lifetime—representing what some might call “overdiagnosis.” Yet there may be some instances in which the DCIS might affect an individual woman’s health. Unfortunately, we can’t prospectively distinguish between the first and the second types of cases.
We follow American College of Obstetricians and Gynecologists and US Preventive Services Task Force guidelines in discussing screening (both its hazards and benefits) with our average-risk patients beginning at age 40. We talk about risk factors for breast cancer, including breast density, but let patients know that no specific additional imaging is advised, and that density is more common in younger women (one consideration in earlier screening) and is quite common in general. Although we do not send follow-up letters to patients with dense breasts, we do educate our staff so that they can respond appropriately should patients call with questions.
Of course, we all bring to the table values that will impact the decisions that we make for ourselves and for our patients. What an ObGyn might suggest may differ from what a radiologist might suggest. Although we follow recommendations made by the radiologist at screening, an ObGyn wants to take care of the whole human being. We are concerned with bones, heart, everything about the patient, so we approach a patient in a different way. These priorities are reflected in the current varying breast cancer screening guidelines.
Continue to: Research on breast cancer screening varies by design...
Research on breast cancer screening varies by design
There has not been a randomized clinical trial conducted on screening mammography since the days of the analog mammogram. The research that has been conducted is difficult to compare due to variations in screening ages and intervals, technology sensitivity, and patient adherence with recommended screening. Treatments for breast cancer also have changed dramatically over time, so the findings of older studies may no longer be relevant to current breast cancer screening. The kind of analysis that needs to be done is an interrupted time series, where you can look at the trajectory of breast cancer survival and whether screening mammography shifts that survival in any way.
One specific study from Australia measured the impact of newer available breast cancer treatments, including tamoxifen for women with receptor-positive tumors and newer chemotherapy strategies.5 The authors analyzed screening mammography trends in one large province where women aged 50 to 69 were offered biennial screening. Trends from the 1990s showed that more women were being screened over time. Simultaneously, however, advances in therapy were entering clinical practice. The researchers pointed to a substantial decline in mortality from breast cancer from the early 1980s until 2013. But their conclusion was that none of the decline in mortality for breast cancer could be attributed to screening mammography when they looked at time trends; from their perspective all of the important decline in breast cancer mortality resulted from better treatment. They concluded that government programs should not support screening mammography.5
That is a recommendation that we do not support. However, we do recognize the conundrum that mammography is less sensitive among those who have dense breasts. In order to have congruent professional guidelines, we support research funding to determine which types, starting ages, and intervals of screening would be best in various patient populations. The USPSTF cites data from studies performed in the 1980s based on outdated technology; more recent (and relevant) randomized clinical trials have not been performed, and yet this information is critical to provide sufficient evidence to develop appropriate guidelines.
Our recommendations for gathering new data
The kind of data we would find most valuable would assess how different screening strategies impact overall mortality and breast cancer-specific mortality. It would require decades of follow-up—which of course means that screening technology will change over that time. A surrogate for evaluating overall survival is to look at interval cancers, which are all breast cancers diagnosed following negative mammograms and prior to the next screening. These cancers may or may not be biologically active, again focusing us on the need to look at overall survival of the patient. In addition, reducing breast cancer mortality may not reduce overall mortality, because the treatment for breast cancer may cause heart disease, or osteoporosis, or something else that impacts overall survival. These are important considerations for women and physicians who are making choices on treatment. What matters to a patient are 2 overlapping questions:
- Do I have a life-threatening condition or do I not?
- Has screening identified a condition that might lead to treatment that’s unnecessary?
The problem is that with breast cancer we can’t tell the difference. We do not understand the biological potential of a lesion when we evaluate an image on MRI, or computed tomography (CT), or mammography.
A re-look at presented data
A trial conducted by Bakker and colleagues6 was discussed by the authors of the DenseBreast-info.org quiz in which they recommended breast MRI for all women with extremely dense breasts (but no other risk factors for breast cancer) detected on screening mammograms.7 The Bakker study was large and conducted in the Netherlands. The primary outcome of the trial was to compare the incidence of interval breast cancers of women aged 50 to 75 randomly assigned to MRI versus those assigned to continued screening mammography every 2 years. Importantly, among the more than 8,000 women who were assigned to MRI, 59%, or fewer than two-thirds, chose to actually undergo MRI.
Among women randomized to MRI, 20 interval cancers were found—4 were diagnosed in those who actually had MRIs, and 16 were diagnosed among women who were randomized to MRI but didn’t undergo the study. Among women assigned to screening mammography only, 161 interval cancers were diagnosed among more than 32,000 women screened. The primary outcome findings were 2.5 interval cancers per 1,000 screenings among women randomly assigned to MRI, and 5 interval cancers per 1,000 screenings among those randomly assigned to mammography only.6
Because the trial included women aged 50 and older, we can’t apply these results to younger women, who often undergo screening mammography in the United States. In addition, the majority of the population in the Netherlands are of Western European ethnicity, a less-diverse population of women than in the United States. Furthermore, among the tumors that were detected in the MRI group, a larger proportion were DCIS, early-stage tumors, well differentiated, and hormone receptor-positive. This observation supports that many of the MRI-detected tumors were cases of overdiagnosis, or the detection of tumors destined not to cause clinical problems for the patient during her lifetime, or for which earlier diagnosis would impact survival.
We also know that treatment of these small ER-positive tumors carries risks for patients, as we may treat them by depriving a patient of estrogen for the rest of her life, with potential consequences of sexual dysfunction, osteoporosis, and perhaps cardiovascular disease depending on her age at the time of that diagnosis. Weighing the risks and benefits of not only treatment but also use of more sensitive screening techniques such as MRI is extremely important. Although Bakker and colleagues’ study results are interesting, we do not feel they support routinely recommending MRI for women found to have extremely dense breasts with mammography.
Overdiagnosis: A difficult concept
One reason overdiagnosis is so challenging to understand is that it can’t be directly measured, which makes comprehending it that much more problematic for clinicians and our patients.
One way to help grasp the overall issue is to compare screening mammography with cervical and colon cancer screening.
We are well aware that cervical cancer screening has reduced the incidence of mortality from invasive cervical cancer.8 We can argue very validly that the biggest success in any cancer screening program in history and globally has been cervical cancer screening. Our specialty, in particular, should feel proud about this. Screening colonoscopy also has repeatedly been found to reduce colon cancer mortality.9 For breast cancer, decades of media messaging have emphasized the benefits of screening mammograms; however, in contrast with cervical cancer screening and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic or advanced disease. Danish authors pointed out in 2017 that screening mammography has not achieved the hoped for or the promised reduction in breast cancer mortality.10
A report published in the March 2022, issue of Annals of Internal Medicine used modeling techniques to estimate the incidence of overdiagnosis and concluded that, among women aged 50-74 years receiving biennial screening mammograms (consistent with USPSTF recommendations), more than 15% of screen-detected breast cancers would represent cases of overdiagnosis. Of note, the study authors found that, among screen-detected cancers, the proportion representing overdiagnosis among women in their 60s (16.7%) and early 70s (23.6%) was higher than among women in their 50s-60s (11.5%-11.6%).11
The former Chief Medical and Scientific Officer for the American Cancer Society Otis Brawley, MD, has stated that, at the same time that breast cancer screening should not be abandoned, “We must acknowledge that overdiagnosis is common. The benefits of screening have been overstated, and some patients considered as ‘cured’ from breast cancer have, in fact, been harmed by unneeded treatment.”12
“Everybody loves early detection,” said Donald Berry, PhD, from MD Anderson Cancer Center, “but it comes with harms.” He points out that mortality rates have improved for breast cancer, but he attributes it to improved treatment. “The harms [of screening] we know, but the benefits of screening are very uncertain.”13
The importance of health equity is receiving more attention. When examining equity according to breast cancer mortality, ethnic minority populations have worse cancer survival outcomes than White women; the mortality rate is 40% higher among Black women than among White women.1 Lower survival rates are also noted among lower socioeconomic groups and among women who live in rural areas. Lower survival rates among ethnic minority women are also noted for cervical and colorectal cancers.2
In the past, these disparities in mortality were attributed to the historically lower breast cancer screening rates among Black women compared with White women. However, decades of efforts to increase mammography rates have effectively addressed much of the racial/ethnic gap in screening rates.1 In fact, a 2021 study showed Black and Hispanic women to have 6% to 10% higher rates of breast, cervical, and colorectal cancer screening than White women according to US Preventive Services Task Force guidelines.2 The study authors point out that other national data have demonstrated similar results and conclude that “higher cancer mortality among racial/ethnic minority groups will not be reduced solely by increasing rates of cancer screening. Although preventive screenings and timely diagnosis are important elements of prognosis, they are just 2 elements of many along the cancer care continuum that need to be addressed to eliminate disparities in cancer mortality.”
Unfortunately, the randomized trials that have been conducted on mammography have been conducted overwhelmingly in White populations. National registry studies from the Netherlands and Sweden are not representative patient populations for the United States. Recently, the US government proposed an ambitious plan to cut cancer mortality rates and has promised vast amounts of research funding to achieve that goal.3 Hopefully, this funding will support studies which enroll diverse patient populations. We hope to gain knowledge on what elements along the cancer care continuum can be addressed to better reduce or eliminate cancer mortality inequities.
References
1. National Cancer Institute. SEER Explorer. https://seer.cancer.gov/explorer/. Accessed February 9, 2022.
2. Benavidez GA, Zgodic A, Zahnd WE, Eberth JM. Disparities in Meeting USPSTF Breast, Cervical, and Colorectal Cancer Screening Guidelines Among Women in the United States. Prev Chronic Dis. 2021;18:200315. doi: http://dx.doi.org/10.5888/pcd18.200315.
3. Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
Continue to: Limitations of breast MRI...
Limitations of breast MRI
Overall, MRI is a diagnostic and monitoring test. It is costlier than mammography, and because it is not recommended in guidelines as a screening modality for most women, it is not typically covered by insurance. Abbreviated (rapid) MRI is a non-standardized imaging strategy being used at a few health centers. It has a shorter protocol overall than MRI, so it takes less time than current MRI and is less expensive, but there are few data on sensitivity and specificity. It is yet to be determined which populations could benefit from this newer technology.
As mentioned, 41% of women in the Bakker et al trial who were randomly assigned to breast MRI chose not to proceed with that exam even though it would have been at no cost to them.6 Anecdotally, some patients who have undergone MRI say they would forgo it a second time as a screening modality because it was a very unpleasant, stressful experience. It’s not a perfect test, although it is more sensitive than mammography.
Other options for following up dense-breast screening. Besides MRI and abbreviated MRI, the following modalities can be used to evaluate women found to have dense breasts with screening mammograms: CT mammography with contrast, molecular breast imaging, and ultrasonography.
Screening and treatment advances
3D mammography. In the US, the great majority of screening mammography now is performed with tomosynthesis, or what our patients sometimes call 3D mammography. In fact, it is approaching standard of care. Women whose screening mammography includes tomosynthesis are less likely to experience a so-called callback for additional imaging with diagnostic mammography or breast ultrasonography.14
Liquid biopsy. A potential major advancement for making decisions about when to treat cancers in general involves determining the biological behavior of a tumor, based on analysis of either circulating tumor DNA or proteins in the blood. As more experience with this new technology accumulates, the role of liquid biopsies for breast cancer will expand.15 Liquid biopsies for screening remain investigational for now, but they hold tremendous potential.
Noninvasive proteomics. With the development of noninvasive proteomic biomarkers obtained from blood, saliva, or nipple aspiration fluid, there exists the possibility of not just evaluating an image of a tumor seen on a mammogram, but actually studying the biological characteristics of that lesion.16 The cost of this technology is far less in terms of resources than MRI or molecular-based imaging, and actually reveals the flaws with using image-based screening. With proteomics, we can tell whether or not a lump is generating proteins that are going to make that disease biologically meaningful, and treatment decisions can be based on that information. This idea has the potential to disrupt our current breast cancer screening paradigm.
Advocacy’s role in mandating legislation
Many advocacy groups lobby on Capitol Hill for legislation related to health care, but we don’t feel that is the best way to make scientific decisions, and it’s not the way to do medicine. Passionate people, who truly believe that their outcome would have been different had something else been done, have every right to advocate, and should. However, without longer-term data focusing on breast cancer and overall mortality, rather than surrogate outcomes like interval cancers, it is not clear that routinely recommending supplemental MRI will improve survival for women with extremely dense breasts. Unfortunately, overall, earlier diagnosis of highly aggressive breast cancer tumors does not result in better outcomes for patients. ●
We have been interested in the quiz series focused on breast cancer screening for women with dense breasts presented in
The concerns with breast cancer in particular
Breast cancer is not cervical cancer. It isn’t one disease. It is a multitude of diseases that happen to show up in the breast. Some are relatively slow-growing—the kinds of cancers that lend themselves to screening and to early intervention. But other cancers are rapidly-growing; they show up no matter how often or what modality we use for screening. Our goal should be to find an approach to screening that can diagnose breast cancer at a stage where we can intervene and positively impact breast cancer specific and overall mortality.
Screening guidelines vary
The variety of screening guidelines published by different professional organizations reflect differing assumptions and sets of values related to the early diagnosis and treatment of breast cancer. (For a comprehensive table of current screening guidelines, see https://www.cdc.gov/cancer/breast/pdf/breast-cancer-screening-guidelines-508.pdf.)
ACOG’s approach—to offer screening at age 40 but to begin by at least age 50 and, through shared decision making with the patient, screen every 1 or 2 years—is focused on capturing as many cases as we can identify, while minimizing the harms of false-positives.1 The perspective of the US Preventive Services Task Force (USPSTF) recommendations (to screen every 2 years beginning at age 50) is at the population level, a cost-effective approach that will have the greatest benefit while minimizing harms in the population at large.2 The American Society of Breast Surgeons recommends screening to begin by age 40.3 Like the breast surgeons, radiologists dedicated to breast imaging are focused on an individual rather than a population level. They strive to identify each and every instance of possible cancer, and therefore recommend annual screening beginning at age 40.4 However, with more aggressive screening in average-risk women many cases of ductal carcinoma in situ (DCIS) are identified—a lesion that, if not detected, may not impact the woman’s health during her lifetime—representing what some might call “overdiagnosis.” Yet there may be some instances in which the DCIS might affect an individual woman’s health. Unfortunately, we can’t prospectively distinguish between the first and the second types of cases.
We follow American College of Obstetricians and Gynecologists and US Preventive Services Task Force guidelines in discussing screening (both its hazards and benefits) with our average-risk patients beginning at age 40. We talk about risk factors for breast cancer, including breast density, but let patients know that no specific additional imaging is advised, and that density is more common in younger women (one consideration in earlier screening) and is quite common in general. Although we do not send follow-up letters to patients with dense breasts, we do educate our staff so that they can respond appropriately should patients call with questions.
Of course, we all bring to the table values that will impact the decisions that we make for ourselves and for our patients. What an ObGyn might suggest may differ from what a radiologist might suggest. Although we follow recommendations made by the radiologist at screening, an ObGyn wants to take care of the whole human being. We are concerned with bones, heart, everything about the patient, so we approach a patient in a different way. These priorities are reflected in the current varying breast cancer screening guidelines.
Continue to: Research on breast cancer screening varies by design...
Research on breast cancer screening varies by design
There has not been a randomized clinical trial conducted on screening mammography since the days of the analog mammogram. The research that has been conducted is difficult to compare due to variations in screening ages and intervals, technology sensitivity, and patient adherence with recommended screening. Treatments for breast cancer also have changed dramatically over time, so the findings of older studies may no longer be relevant to current breast cancer screening. The kind of analysis that needs to be done is an interrupted time series, where you can look at the trajectory of breast cancer survival and whether screening mammography shifts that survival in any way.
One specific study from Australia measured the impact of newer available breast cancer treatments, including tamoxifen for women with receptor-positive tumors and newer chemotherapy strategies.5 The authors analyzed screening mammography trends in one large province where women aged 50 to 69 were offered biennial screening. Trends from the 1990s showed that more women were being screened over time. Simultaneously, however, advances in therapy were entering clinical practice. The researchers pointed to a substantial decline in mortality from breast cancer from the early 1980s until 2013. But their conclusion was that none of the decline in mortality for breast cancer could be attributed to screening mammography when they looked at time trends; from their perspective all of the important decline in breast cancer mortality resulted from better treatment. They concluded that government programs should not support screening mammography.5
That is a recommendation that we do not support. However, we do recognize the conundrum that mammography is less sensitive among those who have dense breasts. In order to have congruent professional guidelines, we support research funding to determine which types, starting ages, and intervals of screening would be best in various patient populations. The USPSTF cites data from studies performed in the 1980s based on outdated technology; more recent (and relevant) randomized clinical trials have not been performed, and yet this information is critical to provide sufficient evidence to develop appropriate guidelines.
Our recommendations for gathering new data
The kind of data we would find most valuable would assess how different screening strategies impact overall mortality and breast cancer-specific mortality. It would require decades of follow-up—which of course means that screening technology will change over that time. A surrogate for evaluating overall survival is to look at interval cancers, which are all breast cancers diagnosed following negative mammograms and prior to the next screening. These cancers may or may not be biologically active, again focusing us on the need to look at overall survival of the patient. In addition, reducing breast cancer mortality may not reduce overall mortality, because the treatment for breast cancer may cause heart disease, or osteoporosis, or something else that impacts overall survival. These are important considerations for women and physicians who are making choices on treatment. What matters to a patient are 2 overlapping questions:
- Do I have a life-threatening condition or do I not?
- Has screening identified a condition that might lead to treatment that’s unnecessary?
The problem is that with breast cancer we can’t tell the difference. We do not understand the biological potential of a lesion when we evaluate an image on MRI, or computed tomography (CT), or mammography.
A re-look at presented data
A trial conducted by Bakker and colleagues6 was discussed by the authors of the DenseBreast-info.org quiz in which they recommended breast MRI for all women with extremely dense breasts (but no other risk factors for breast cancer) detected on screening mammograms.7 The Bakker study was large and conducted in the Netherlands. The primary outcome of the trial was to compare the incidence of interval breast cancers of women aged 50 to 75 randomly assigned to MRI versus those assigned to continued screening mammography every 2 years. Importantly, among the more than 8,000 women who were assigned to MRI, 59%, or fewer than two-thirds, chose to actually undergo MRI.
Among women randomized to MRI, 20 interval cancers were found—4 were diagnosed in those who actually had MRIs, and 16 were diagnosed among women who were randomized to MRI but didn’t undergo the study. Among women assigned to screening mammography only, 161 interval cancers were diagnosed among more than 32,000 women screened. The primary outcome findings were 2.5 interval cancers per 1,000 screenings among women randomly assigned to MRI, and 5 interval cancers per 1,000 screenings among those randomly assigned to mammography only.6
Because the trial included women aged 50 and older, we can’t apply these results to younger women, who often undergo screening mammography in the United States. In addition, the majority of the population in the Netherlands are of Western European ethnicity, a less-diverse population of women than in the United States. Furthermore, among the tumors that were detected in the MRI group, a larger proportion were DCIS, early-stage tumors, well differentiated, and hormone receptor-positive. This observation supports that many of the MRI-detected tumors were cases of overdiagnosis, or the detection of tumors destined not to cause clinical problems for the patient during her lifetime, or for which earlier diagnosis would impact survival.
We also know that treatment of these small ER-positive tumors carries risks for patients, as we may treat them by depriving a patient of estrogen for the rest of her life, with potential consequences of sexual dysfunction, osteoporosis, and perhaps cardiovascular disease depending on her age at the time of that diagnosis. Weighing the risks and benefits of not only treatment but also use of more sensitive screening techniques such as MRI is extremely important. Although Bakker and colleagues’ study results are interesting, we do not feel they support routinely recommending MRI for women found to have extremely dense breasts with mammography.
Overdiagnosis: A difficult concept
One reason overdiagnosis is so challenging to understand is that it can’t be directly measured, which makes comprehending it that much more problematic for clinicians and our patients.
One way to help grasp the overall issue is to compare screening mammography with cervical and colon cancer screening.
We are well aware that cervical cancer screening has reduced the incidence of mortality from invasive cervical cancer.8 We can argue very validly that the biggest success in any cancer screening program in history and globally has been cervical cancer screening. Our specialty, in particular, should feel proud about this. Screening colonoscopy also has repeatedly been found to reduce colon cancer mortality.9 For breast cancer, decades of media messaging have emphasized the benefits of screening mammograms; however, in contrast with cervical cancer screening and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic or advanced disease. Danish authors pointed out in 2017 that screening mammography has not achieved the hoped for or the promised reduction in breast cancer mortality.10
A report published in the March 2022, issue of Annals of Internal Medicine used modeling techniques to estimate the incidence of overdiagnosis and concluded that, among women aged 50-74 years receiving biennial screening mammograms (consistent with USPSTF recommendations), more than 15% of screen-detected breast cancers would represent cases of overdiagnosis. Of note, the study authors found that, among screen-detected cancers, the proportion representing overdiagnosis among women in their 60s (16.7%) and early 70s (23.6%) was higher than among women in their 50s-60s (11.5%-11.6%).11
The former Chief Medical and Scientific Officer for the American Cancer Society Otis Brawley, MD, has stated that, at the same time that breast cancer screening should not be abandoned, “We must acknowledge that overdiagnosis is common. The benefits of screening have been overstated, and some patients considered as ‘cured’ from breast cancer have, in fact, been harmed by unneeded treatment.”12
“Everybody loves early detection,” said Donald Berry, PhD, from MD Anderson Cancer Center, “but it comes with harms.” He points out that mortality rates have improved for breast cancer, but he attributes it to improved treatment. “The harms [of screening] we know, but the benefits of screening are very uncertain.”13
The importance of health equity is receiving more attention. When examining equity according to breast cancer mortality, ethnic minority populations have worse cancer survival outcomes than White women; the mortality rate is 40% higher among Black women than among White women.1 Lower survival rates are also noted among lower socioeconomic groups and among women who live in rural areas. Lower survival rates among ethnic minority women are also noted for cervical and colorectal cancers.2
In the past, these disparities in mortality were attributed to the historically lower breast cancer screening rates among Black women compared with White women. However, decades of efforts to increase mammography rates have effectively addressed much of the racial/ethnic gap in screening rates.1 In fact, a 2021 study showed Black and Hispanic women to have 6% to 10% higher rates of breast, cervical, and colorectal cancer screening than White women according to US Preventive Services Task Force guidelines.2 The study authors point out that other national data have demonstrated similar results and conclude that “higher cancer mortality among racial/ethnic minority groups will not be reduced solely by increasing rates of cancer screening. Although preventive screenings and timely diagnosis are important elements of prognosis, they are just 2 elements of many along the cancer care continuum that need to be addressed to eliminate disparities in cancer mortality.”
Unfortunately, the randomized trials that have been conducted on mammography have been conducted overwhelmingly in White populations. National registry studies from the Netherlands and Sweden are not representative patient populations for the United States. Recently, the US government proposed an ambitious plan to cut cancer mortality rates and has promised vast amounts of research funding to achieve that goal.3 Hopefully, this funding will support studies which enroll diverse patient populations. We hope to gain knowledge on what elements along the cancer care continuum can be addressed to better reduce or eliminate cancer mortality inequities.
References
1. National Cancer Institute. SEER Explorer. https://seer.cancer.gov/explorer/. Accessed February 9, 2022.
2. Benavidez GA, Zgodic A, Zahnd WE, Eberth JM. Disparities in Meeting USPSTF Breast, Cervical, and Colorectal Cancer Screening Guidelines Among Women in the United States. Prev Chronic Dis. 2021;18:200315. doi: http://dx.doi.org/10.5888/pcd18.200315.
3. Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
Continue to: Limitations of breast MRI...
Limitations of breast MRI
Overall, MRI is a diagnostic and monitoring test. It is costlier than mammography, and because it is not recommended in guidelines as a screening modality for most women, it is not typically covered by insurance. Abbreviated (rapid) MRI is a non-standardized imaging strategy being used at a few health centers. It has a shorter protocol overall than MRI, so it takes less time than current MRI and is less expensive, but there are few data on sensitivity and specificity. It is yet to be determined which populations could benefit from this newer technology.
As mentioned, 41% of women in the Bakker et al trial who were randomly assigned to breast MRI chose not to proceed with that exam even though it would have been at no cost to them.6 Anecdotally, some patients who have undergone MRI say they would forgo it a second time as a screening modality because it was a very unpleasant, stressful experience. It’s not a perfect test, although it is more sensitive than mammography.
Other options for following up dense-breast screening. Besides MRI and abbreviated MRI, the following modalities can be used to evaluate women found to have dense breasts with screening mammograms: CT mammography with contrast, molecular breast imaging, and ultrasonography.
Screening and treatment advances
3D mammography. In the US, the great majority of screening mammography now is performed with tomosynthesis, or what our patients sometimes call 3D mammography. In fact, it is approaching standard of care. Women whose screening mammography includes tomosynthesis are less likely to experience a so-called callback for additional imaging with diagnostic mammography or breast ultrasonography.14
Liquid biopsy. A potential major advancement for making decisions about when to treat cancers in general involves determining the biological behavior of a tumor, based on analysis of either circulating tumor DNA or proteins in the blood. As more experience with this new technology accumulates, the role of liquid biopsies for breast cancer will expand.15 Liquid biopsies for screening remain investigational for now, but they hold tremendous potential.
Noninvasive proteomics. With the development of noninvasive proteomic biomarkers obtained from blood, saliva, or nipple aspiration fluid, there exists the possibility of not just evaluating an image of a tumor seen on a mammogram, but actually studying the biological characteristics of that lesion.16 The cost of this technology is far less in terms of resources than MRI or molecular-based imaging, and actually reveals the flaws with using image-based screening. With proteomics, we can tell whether or not a lump is generating proteins that are going to make that disease biologically meaningful, and treatment decisions can be based on that information. This idea has the potential to disrupt our current breast cancer screening paradigm.
Advocacy’s role in mandating legislation
Many advocacy groups lobby on Capitol Hill for legislation related to health care, but we don’t feel that is the best way to make scientific decisions, and it’s not the way to do medicine. Passionate people, who truly believe that their outcome would have been different had something else been done, have every right to advocate, and should. However, without longer-term data focusing on breast cancer and overall mortality, rather than surrogate outcomes like interval cancers, it is not clear that routinely recommending supplemental MRI will improve survival for women with extremely dense breasts. Unfortunately, overall, earlier diagnosis of highly aggressive breast cancer tumors does not result in better outcomes for patients. ●
- American College of Obstetricians and Gynecologists. Practice Bulletin number 179: breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130: e1-e16. doi: 10.1097/AOG.0000000000002158.
- Sui AL, U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:279-296. doi: 10.7326/M15-2886.
- The American Society of Breast Surgeons. Position statement on screening mammography. https://www.breastsurgeons.org/docs /statements/Position-Statement-on-ScreeningMammography.pdf. Accessed February 15, 2022.
- Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average-risk: update from the ACR and Society of Breast Imaging. J Am College Radiol. 2021;18:1280-1288.
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020;3:e208249.
- Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102. doi: 10.1056/NEJMoa1903986.
- Seitzman R, Berg W. Average-risk women with dense breasts—what breast screening is appropriate? OBG Manag. 2021;33:18-19. doi: 10.12788/obgm.0155.
- Gopalani SV, Janitz AE, Campbell JE. Cervical cancer incidence and mortality among non-hispanic African American and White women, United States, 1999-2015. J Natl Med Assoc. 2020;112:632-638. doi: 10.1016 /j.jnma.2020.06.007.
- Niikura R, Hirata Y, Suzuki N, et al. Colonoscopy reduces colorectal cancer mortality: a multicenter, long-term, colonoscopy-based cohort study. PLoS One. 2017;12:e0185294.
- Jørgensen KJ, Gøtzsche PC, Kalager M, et al. Breast cancer screening in Denmark. Ann Intern Med. 2017;167:524. doi: 10.7326/L17-0270.
- Ryser MD, Lange J, Inoue IL, et al. Estimation of breast cancer overdiagnosis in a U.S. breast screening cohort. Ann Intern Med. 2022 March 1. doi: 10.7326/M21-3577.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis. Ann Intern Med. 2017;166:364-365. doi:10.7326/M16-2850.
- Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
- Conant EF, Barlow WE, Herschorn SD, et al. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-642. doi: 10.1001 /jamaoncol.2018.7078.
- Tay TK, Tan PH. Liquid biopsy in breast cancer: a focused review. Arch Pathol Lab Med. 2021;145: 678-686. doi: 10.5858/arpa.2019-0559-RA.
- Debald M, Wolgarten M, Walgenbach-Brunagel G, et al. Non-invasive proteomics—thinking about personalized breast cancer screening and treatment. EPMA J. 2010;1:413-420. doi: 10.1007 /s13167-010-0039-9.
- American College of Obstetricians and Gynecologists. Practice Bulletin number 179: breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130: e1-e16. doi: 10.1097/AOG.0000000000002158.
- Sui AL, U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:279-296. doi: 10.7326/M15-2886.
- The American Society of Breast Surgeons. Position statement on screening mammography. https://www.breastsurgeons.org/docs /statements/Position-Statement-on-ScreeningMammography.pdf. Accessed February 15, 2022.
- Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average-risk: update from the ACR and Society of Breast Imaging. J Am College Radiol. 2021;18:1280-1288.
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020;3:e208249.
- Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102. doi: 10.1056/NEJMoa1903986.
- Seitzman R, Berg W. Average-risk women with dense breasts—what breast screening is appropriate? OBG Manag. 2021;33:18-19. doi: 10.12788/obgm.0155.
- Gopalani SV, Janitz AE, Campbell JE. Cervical cancer incidence and mortality among non-hispanic African American and White women, United States, 1999-2015. J Natl Med Assoc. 2020;112:632-638. doi: 10.1016 /j.jnma.2020.06.007.
- Niikura R, Hirata Y, Suzuki N, et al. Colonoscopy reduces colorectal cancer mortality: a multicenter, long-term, colonoscopy-based cohort study. PLoS One. 2017;12:e0185294.
- Jørgensen KJ, Gøtzsche PC, Kalager M, et al. Breast cancer screening in Denmark. Ann Intern Med. 2017;167:524. doi: 10.7326/L17-0270.
- Ryser MD, Lange J, Inoue IL, et al. Estimation of breast cancer overdiagnosis in a U.S. breast screening cohort. Ann Intern Med. 2022 March 1. doi: 10.7326/M21-3577.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis. Ann Intern Med. 2017;166:364-365. doi:10.7326/M16-2850.
- Stohlberg SG, Kolata G. Biden presents ambitious plan to cut cancer death rate in half. The New York Times. February 2, 2022.
- Conant EF, Barlow WE, Herschorn SD, et al. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-642. doi: 10.1001 /jamaoncol.2018.7078.
- Tay TK, Tan PH. Liquid biopsy in breast cancer: a focused review. Arch Pathol Lab Med. 2021;145: 678-686. doi: 10.5858/arpa.2019-0559-RA.
- Debald M, Wolgarten M, Walgenbach-Brunagel G, et al. Non-invasive proteomics—thinking about personalized breast cancer screening and treatment. EPMA J. 2010;1:413-420. doi: 10.1007 /s13167-010-0039-9.
Pharma should stop doing business in Russia, says ethicist
Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?
Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.
I think both arguments fail.
We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?
Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.
To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.
“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”
The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.
Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.
There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.
How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.
Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.
The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.
Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.
Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.
A version of this article first appeared on Medscape.com.
Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?
Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.
I think both arguments fail.
We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?
Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.
To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.
“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”
The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.
Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.
There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.
How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.
Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.
The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.
Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.
Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.
A version of this article first appeared on Medscape.com.
Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?
Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.
I think both arguments fail.
We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?
Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.
To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.
“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”
The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.
Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.
There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.
How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.
Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.
The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.
Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.
Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.
A version of this article first appeared on Medscape.com.
