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Morinda citrifolia (Noni) tree: Many names, even more applications
, which has been in use on the islands for two millennia.1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.4-6 It is also deployed for a wide range of health purposes in Brazil.7
Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.8 This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
Diverse biologic properties
In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.1
Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.9
In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.3
A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.7
Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.2
Photoprotection and antiaging potential
Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.10
In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.11
A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.12
Conclusion
Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.
Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com.
References
1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.
2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.
3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.
4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.
5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.
6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.
7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.
8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.
9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.
11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.
12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.
, which has been in use on the islands for two millennia.1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.4-6 It is also deployed for a wide range of health purposes in Brazil.7
Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.8 This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
Diverse biologic properties
In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.1
Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.9
In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.3
A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.7
Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.2
Photoprotection and antiaging potential
Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.10
In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.11
A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.12
Conclusion
Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.
Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com.
References
1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.
2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.
3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.
4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.
5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.
6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.
7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.
8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.
9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.
11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.
12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.
, which has been in use on the islands for two millennia.1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.4-6 It is also deployed for a wide range of health purposes in Brazil.7
Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.8 This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
Diverse biologic properties
In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.1
Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.9
In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.3
A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.7
Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.2
Photoprotection and antiaging potential
Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.10
In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.11
A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.12
Conclusion
Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.
Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com.
References
1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.
2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.
3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.
4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.
5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.
6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.
7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.
8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.
9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.
11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.
12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.
Being the optimistic physician
Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?
Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).
Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?
Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.
On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.
Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.
However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.
My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?
Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).
Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?
Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.
On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.
Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.
However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.
My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?
Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).
Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?
Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.
On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.
Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.
However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.
My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
CBD for sleep and anxiety – A brief review of the evidence
Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.
Discussion
CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.
In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.1 In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.2
CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.3
- There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
- There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
- Clear information about appropriate dosing for children is limited.
- Varying delivery systems could affect absorption and bioavailability of CBD.
- Information is lacking regarding potential drug-drug interactions.
- There is a lack of information regarding effects of long-term use.
Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at pdnews@mdedge.com.
References
1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.
2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.
3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.
Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.
Discussion
CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.
In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.1 In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.2
CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.3
- There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
- There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
- Clear information about appropriate dosing for children is limited.
- Varying delivery systems could affect absorption and bioavailability of CBD.
- Information is lacking regarding potential drug-drug interactions.
- There is a lack of information regarding effects of long-term use.
Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at pdnews@mdedge.com.
References
1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.
2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.
3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.
Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.
Discussion
CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.
In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.1 In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.2
CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.3
- There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
- There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
- Clear information about appropriate dosing for children is limited.
- Varying delivery systems could affect absorption and bioavailability of CBD.
- Information is lacking regarding potential drug-drug interactions.
- There is a lack of information regarding effects of long-term use.
Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at pdnews@mdedge.com.
References
1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.
2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.
3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.
Educating teens, young adults about dangers of vaping
Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.
Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,1 and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,2 cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.
A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.3 Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.4
Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.
Most of the patients affected are adolescents and young adults, with the average age of 19 years.5 This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.7 Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.
Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.
In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.8-11
Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. As clinicians, we must counter those messages.
Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?
In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
References
1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19.
2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.
3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.
4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.
5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.
6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.
7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.
8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.
9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.
10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.
11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.
* This column was updated 9/24/2019.
Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.
Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,1 and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,2 cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.
A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.3 Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.4
Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.
Most of the patients affected are adolescents and young adults, with the average age of 19 years.5 This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.7 Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.
Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.
In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.8-11
Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. As clinicians, we must counter those messages.
Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?
In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
References
1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19.
2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.
3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.
4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.
5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.
6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.
7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.
8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.
9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.
10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.
11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.
* This column was updated 9/24/2019.
Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.
Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,1 and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,2 cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.
A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.3 Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.4
Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.
Most of the patients affected are adolescents and young adults, with the average age of 19 years.5 This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.7 Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.
Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.
In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.8-11
Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. As clinicians, we must counter those messages.
Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?
In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
References
1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19.
2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.
3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.
4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.
5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.
6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.
7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.
8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.
9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.
10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.
11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.
* This column was updated 9/24/2019.
Review your insurance
Insurance, so goes the hoary cliché, is the one product you buy hoping never to use. While no one enjoys foreseeing unforeseeable calamities, if you haven’t reviewed your insurance coverage recently, there is no time like the present.
, but the cost has become prohibitive in many areas, when insurers are willing to write them at all. “Claims made” policies are cheaper and provide the same protection, but only while coverage is in effect. You will need “tail” coverage against belated claims after your policy lapses, but many companies provide free tail coverage if you are retiring. If you are simply switching workplaces (or policies), ask your new insurer about “nose” coverage, for claims involving acts that occurred before the new policy takes effect.
Other alternatives are gaining popularity as the demand for reasonably priced insurance increases. The most common, known as reciprocal exchanges, are very similar to traditional insurers, but require policyholders to make capital contributions in addition to payment of premiums, at least in their early stages. You get your investment back, with interest, when (if) the exchange becomes solvent.
Another option, called a captive, is a company formed by a consortium of medical practices to write their own insurance policies. All participants are shareholders, and all premiums (less administrative expenses) go toward building the security of the captive. Most captives purchase reinsurance to protect against catastrophic losses. If all goes well, individual owners sell their shares at retirement for a profit, which has grown tax-free in the interim.
Those willing to shoulder more risk might consider a risk retention group (RRG), a sort of combination of an exchange and a captive. Again, the owners are the insureds themselves, but all responsibility for management and adequate funding falls on their shoulders, and reinsurance is not usually an option. Most medical malpractice RRGs are licensed in Vermont or South Carolina, because of favorable laws in those states, but can be based in any state that allows them (36 at this writing). RRGs provide profit opportunities not available with traditional insurance, but there is risk: A few large claims could eat up all the profits, or even put owners in a financial hole.
Malpractice insurance requirements will remain fairly static throughout your career, but other insurance needs evolve over time. A good example is life insurance: As retirement savings increase, the need for life insurance decreases – especially expensive “whole life” coverage, which can often be eliminated or converted to cheaper “term” insurance.
Health insurance premiums continue to soar, but the Affordable Care Act might offer a favorable alternative for your office policy. If you are considering that, the Centers for Medicare & Medicaid Services maintains a website summarizing the various options for employers.
Worker compensation insurance is mandatory in most states and heavily regulated, so there is little wiggle room. However, some states do not require you, as the employer, to cover yourself, so eliminating that coverage could save you a substantial amount. This is only worth considering, of course, if you’re in excellent health and have very good personal health and disability coverage.
Disability insurance is not something to skimp on, but if you are approaching retirement age and have no major health issues, you may be able to decrease your coverage, or even eliminate it entirely if your retirement plan is far enough along.
Liability insurance is likewise no place to pinch pennies, but you might be able to add an “umbrella” policy providing comprehensive catastrophic coverage, which may allow you to decrease your regular coverage, or raise your deductible limits.
Two additional policies to consider are office overhead insurance, to cover the costs of keeping your office open should you be temporarily incapacitated, and employee practices liability insurance (EPLI), which protects you from lawsuits brought by militant or disgruntled employees. I covered EPLI in detail several months ago.
If you are over 50, I strongly recommend long-term-care insurance as well. It’s relatively inexpensive if you buy it while you’re still healthy, and it could save you and your heirs a load of money and aggravation on the other end. If you have shouldered the expense of caring for a chronically ill parent or grandparent, you know what I’m talking about. More about that next month.
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 dermnews@mdedge.com.
Insurance, so goes the hoary cliché, is the one product you buy hoping never to use. While no one enjoys foreseeing unforeseeable calamities, if you haven’t reviewed your insurance coverage recently, there is no time like the present.
, but the cost has become prohibitive in many areas, when insurers are willing to write them at all. “Claims made” policies are cheaper and provide the same protection, but only while coverage is in effect. You will need “tail” coverage against belated claims after your policy lapses, but many companies provide free tail coverage if you are retiring. If you are simply switching workplaces (or policies), ask your new insurer about “nose” coverage, for claims involving acts that occurred before the new policy takes effect.
Other alternatives are gaining popularity as the demand for reasonably priced insurance increases. The most common, known as reciprocal exchanges, are very similar to traditional insurers, but require policyholders to make capital contributions in addition to payment of premiums, at least in their early stages. You get your investment back, with interest, when (if) the exchange becomes solvent.
Another option, called a captive, is a company formed by a consortium of medical practices to write their own insurance policies. All participants are shareholders, and all premiums (less administrative expenses) go toward building the security of the captive. Most captives purchase reinsurance to protect against catastrophic losses. If all goes well, individual owners sell their shares at retirement for a profit, which has grown tax-free in the interim.
Those willing to shoulder more risk might consider a risk retention group (RRG), a sort of combination of an exchange and a captive. Again, the owners are the insureds themselves, but all responsibility for management and adequate funding falls on their shoulders, and reinsurance is not usually an option. Most medical malpractice RRGs are licensed in Vermont or South Carolina, because of favorable laws in those states, but can be based in any state that allows them (36 at this writing). RRGs provide profit opportunities not available with traditional insurance, but there is risk: A few large claims could eat up all the profits, or even put owners in a financial hole.
Malpractice insurance requirements will remain fairly static throughout your career, but other insurance needs evolve over time. A good example is life insurance: As retirement savings increase, the need for life insurance decreases – especially expensive “whole life” coverage, which can often be eliminated or converted to cheaper “term” insurance.
Health insurance premiums continue to soar, but the Affordable Care Act might offer a favorable alternative for your office policy. If you are considering that, the Centers for Medicare & Medicaid Services maintains a website summarizing the various options for employers.
Worker compensation insurance is mandatory in most states and heavily regulated, so there is little wiggle room. However, some states do not require you, as the employer, to cover yourself, so eliminating that coverage could save you a substantial amount. This is only worth considering, of course, if you’re in excellent health and have very good personal health and disability coverage.
Disability insurance is not something to skimp on, but if you are approaching retirement age and have no major health issues, you may be able to decrease your coverage, or even eliminate it entirely if your retirement plan is far enough along.
Liability insurance is likewise no place to pinch pennies, but you might be able to add an “umbrella” policy providing comprehensive catastrophic coverage, which may allow you to decrease your regular coverage, or raise your deductible limits.
Two additional policies to consider are office overhead insurance, to cover the costs of keeping your office open should you be temporarily incapacitated, and employee practices liability insurance (EPLI), which protects you from lawsuits brought by militant or disgruntled employees. I covered EPLI in detail several months ago.
If you are over 50, I strongly recommend long-term-care insurance as well. It’s relatively inexpensive if you buy it while you’re still healthy, and it could save you and your heirs a load of money and aggravation on the other end. If you have shouldered the expense of caring for a chronically ill parent or grandparent, you know what I’m talking about. More about that next month.
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 dermnews@mdedge.com.
Insurance, so goes the hoary cliché, is the one product you buy hoping never to use. While no one enjoys foreseeing unforeseeable calamities, if you haven’t reviewed your insurance coverage recently, there is no time like the present.
, but the cost has become prohibitive in many areas, when insurers are willing to write them at all. “Claims made” policies are cheaper and provide the same protection, but only while coverage is in effect. You will need “tail” coverage against belated claims after your policy lapses, but many companies provide free tail coverage if you are retiring. If you are simply switching workplaces (or policies), ask your new insurer about “nose” coverage, for claims involving acts that occurred before the new policy takes effect.
Other alternatives are gaining popularity as the demand for reasonably priced insurance increases. The most common, known as reciprocal exchanges, are very similar to traditional insurers, but require policyholders to make capital contributions in addition to payment of premiums, at least in their early stages. You get your investment back, with interest, when (if) the exchange becomes solvent.
Another option, called a captive, is a company formed by a consortium of medical practices to write their own insurance policies. All participants are shareholders, and all premiums (less administrative expenses) go toward building the security of the captive. Most captives purchase reinsurance to protect against catastrophic losses. If all goes well, individual owners sell their shares at retirement for a profit, which has grown tax-free in the interim.
Those willing to shoulder more risk might consider a risk retention group (RRG), a sort of combination of an exchange and a captive. Again, the owners are the insureds themselves, but all responsibility for management and adequate funding falls on their shoulders, and reinsurance is not usually an option. Most medical malpractice RRGs are licensed in Vermont or South Carolina, because of favorable laws in those states, but can be based in any state that allows them (36 at this writing). RRGs provide profit opportunities not available with traditional insurance, but there is risk: A few large claims could eat up all the profits, or even put owners in a financial hole.
Malpractice insurance requirements will remain fairly static throughout your career, but other insurance needs evolve over time. A good example is life insurance: As retirement savings increase, the need for life insurance decreases – especially expensive “whole life” coverage, which can often be eliminated or converted to cheaper “term” insurance.
Health insurance premiums continue to soar, but the Affordable Care Act might offer a favorable alternative for your office policy. If you are considering that, the Centers for Medicare & Medicaid Services maintains a website summarizing the various options for employers.
Worker compensation insurance is mandatory in most states and heavily regulated, so there is little wiggle room. However, some states do not require you, as the employer, to cover yourself, so eliminating that coverage could save you a substantial amount. This is only worth considering, of course, if you’re in excellent health and have very good personal health and disability coverage.
Disability insurance is not something to skimp on, but if you are approaching retirement age and have no major health issues, you may be able to decrease your coverage, or even eliminate it entirely if your retirement plan is far enough along.
Liability insurance is likewise no place to pinch pennies, but you might be able to add an “umbrella” policy providing comprehensive catastrophic coverage, which may allow you to decrease your regular coverage, or raise your deductible limits.
Two additional policies to consider are office overhead insurance, to cover the costs of keeping your office open should you be temporarily incapacitated, and employee practices liability insurance (EPLI), which protects you from lawsuits brought by militant or disgruntled employees. I covered EPLI in detail several months ago.
If you are over 50, I strongly recommend long-term-care insurance as well. It’s relatively inexpensive if you buy it while you’re still healthy, and it could save you and your heirs a load of money and aggravation on the other end. If you have shouldered the expense of caring for a chronically ill parent or grandparent, you know what I’m talking about. More about that next month.
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 dermnews@mdedge.com.
Use of genetic testing for congenital heart defect management
The average student in America learns that genes form the building blocks of what makes us human by the time they receive their high school diploma. Indeed, the completion of the Human Genome Project in 2003 paved the way for our genetic makeup, much like our medical history, to become a routine part of our health care. For example, our faculty at the University of Maryland School of Medicine discovered an important gene – CYP2C19 – which is involved in the metabolism of the antiplatelet medicine clopidogrel (Plavix). Although most people have this gene, some don’t. Therefore, when we manage a patient with coronary disease, we use a genetic screen to determine whether that patient has CYP2C19 and then modify therapy based on these results.
Our genes also have become commodities – from companies willing to analyze our genes to determine our racial and ethnic ancestry or propensity for certain diseases to those that can sequence the family dog’s genes.
Advances in genomics similarly have impacted ob.gyn. practice. Because of rapidly evolving gene analysis tools, we can now, for example, noninvasively test a developing fetus’s risk for chromosomal abnormalities and determine a baby’s sex by merely examining fetal DNA in a pregnant woman’s bloodstream. Although not diagnostic, these gene-based prenatal screening tests have reduced the need for unnecessary, costly, and highly invasive procedures for many of our patients.
Importantly, our recognition that certain genes can confer a higher risk of disease has meant that performing a prenatal genetic evaluation can greatly inform the mother and her care team about potential problems her baby may have that may require additional management. For babies who have congenital heart defects, a genetic evaluation performed in addition to sonographic examination can provide ob.gyns. with crucial details to enhance pregnancy management and postnatal care decisions.
The importance of genetic testing and analysis in the detection, treatment, and prevention of congenital heart defects is the topic of part two of this two-part Master Class series authored by Shifa Turan, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. By using a combination of three- and four-dimensional ultrasound with gene assays, Dr. Turan and her colleagues can greatly enhance and personalize the care they deliver to their patients.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
The average student in America learns that genes form the building blocks of what makes us human by the time they receive their high school diploma. Indeed, the completion of the Human Genome Project in 2003 paved the way for our genetic makeup, much like our medical history, to become a routine part of our health care. For example, our faculty at the University of Maryland School of Medicine discovered an important gene – CYP2C19 – which is involved in the metabolism of the antiplatelet medicine clopidogrel (Plavix). Although most people have this gene, some don’t. Therefore, when we manage a patient with coronary disease, we use a genetic screen to determine whether that patient has CYP2C19 and then modify therapy based on these results.
Our genes also have become commodities – from companies willing to analyze our genes to determine our racial and ethnic ancestry or propensity for certain diseases to those that can sequence the family dog’s genes.
Advances in genomics similarly have impacted ob.gyn. practice. Because of rapidly evolving gene analysis tools, we can now, for example, noninvasively test a developing fetus’s risk for chromosomal abnormalities and determine a baby’s sex by merely examining fetal DNA in a pregnant woman’s bloodstream. Although not diagnostic, these gene-based prenatal screening tests have reduced the need for unnecessary, costly, and highly invasive procedures for many of our patients.
Importantly, our recognition that certain genes can confer a higher risk of disease has meant that performing a prenatal genetic evaluation can greatly inform the mother and her care team about potential problems her baby may have that may require additional management. For babies who have congenital heart defects, a genetic evaluation performed in addition to sonographic examination can provide ob.gyns. with crucial details to enhance pregnancy management and postnatal care decisions.
The importance of genetic testing and analysis in the detection, treatment, and prevention of congenital heart defects is the topic of part two of this two-part Master Class series authored by Shifa Turan, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. By using a combination of three- and four-dimensional ultrasound with gene assays, Dr. Turan and her colleagues can greatly enhance and personalize the care they deliver to their patients.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
The average student in America learns that genes form the building blocks of what makes us human by the time they receive their high school diploma. Indeed, the completion of the Human Genome Project in 2003 paved the way for our genetic makeup, much like our medical history, to become a routine part of our health care. For example, our faculty at the University of Maryland School of Medicine discovered an important gene – CYP2C19 – which is involved in the metabolism of the antiplatelet medicine clopidogrel (Plavix). Although most people have this gene, some don’t. Therefore, when we manage a patient with coronary disease, we use a genetic screen to determine whether that patient has CYP2C19 and then modify therapy based on these results.
Our genes also have become commodities – from companies willing to analyze our genes to determine our racial and ethnic ancestry or propensity for certain diseases to those that can sequence the family dog’s genes.
Advances in genomics similarly have impacted ob.gyn. practice. Because of rapidly evolving gene analysis tools, we can now, for example, noninvasively test a developing fetus’s risk for chromosomal abnormalities and determine a baby’s sex by merely examining fetal DNA in a pregnant woman’s bloodstream. Although not diagnostic, these gene-based prenatal screening tests have reduced the need for unnecessary, costly, and highly invasive procedures for many of our patients.
Importantly, our recognition that certain genes can confer a higher risk of disease has meant that performing a prenatal genetic evaluation can greatly inform the mother and her care team about potential problems her baby may have that may require additional management. For babies who have congenital heart defects, a genetic evaluation performed in addition to sonographic examination can provide ob.gyns. with crucial details to enhance pregnancy management and postnatal care decisions.
The importance of genetic testing and analysis in the detection, treatment, and prevention of congenital heart defects is the topic of part two of this two-part Master Class series authored by Shifa Turan, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. By using a combination of three- and four-dimensional ultrasound with gene assays, Dr. Turan and her colleagues can greatly enhance and personalize the care they deliver to their patients.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
Genetic assessment for CHD: Case-specific, stepwise
Congenital heart defects (CHDs) are etiologically heterogeneous, but in recent years it has become clear that genetics plays a larger role in the development of CHDs than was previously thought. Research has been shifting from a focus on risk – estimating the magnitude of increased risk, for instance, based on maternal or familial risk factors – to a focus on the etiology of cardiac defects.
In practice, advances in genetic testing technologies have made the underlying causes of CHDs increasingly detectable. Chromosomal microarray analysis (CMA) – technology that detects significantly more and smaller changes in the amount of chromosomal material than traditional karyotype – has been proven to increase the diagnostic yield in cases of isolated CHDs and CHDs with extracardiac anomalies. Targeted next-generation sequencing also is now available as an additional approach in selective cases, and a clinically viable option for whole-exome sequencing is fast approaching.
For researchers, genetic evaluation carries the potential to unravel remaining mysteries about underlying causes of CHDs – to provide pathological insights and identify potential therapeutic targets. Currently, about 6 % of the total pie of presumed genetic determinants of CHDs is attributed to chromosomal anomalies, 10% to copy number variants, and 12% to single-gene defects. The remaining 72% of etiology, approximately, is undetermined.
As Helen Taussig, MD, (known as the founder of pediatric cardiology) once said, common cardiac malformations occurring in otherwise “normal” individuals “must be genetic in origin.”1 Greater use of genetic testing – and in particular, of whole-exome sequencing – will drive down this “undetermined” piece of the genetics pie.
For clinicians and patients, prenatal genetic evaluation can inform clinical management, guiding decisions on the mode, timing, and location of delivery. Genetic assessments help guide the neonatal health care team in taking optimal care of the infant, and the surgeon in preparing for neonatal surgeries and postsurgical complications.
In a recent analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database, prenatal diagnosis was associated with a lower overall prevalence of major preoperative risk factors for cardiac surgery.2 Surgical outcomes themselves also have been shown to be better after the prenatal diagnosis of complex CHDs, mainly because of improvements in perioperative care.3
When genetic etiology is elucidated, the cardiologist also is better able to counsel patients about anticipated challenges – such as the propensity, with certain genetic variants of CHD, to develop neurodevelopmental delays or other cardiac complications – and to target patient follow-up. Patients also can make informed decisions about termination or continuation of a current pregnancy and about family planning in the future.
Fortunately, advances in genetics technology have paralleled technological advancements in ultrasound. As I discussed in part one of this two-part Master Class series, it is now possible to detect many major CHDs well before 16 weeks’ gestation. Checking the structure of the fetal heart at the first-trimester screening and sonography (11-14 weeks of gestation) offers the opportunity for early genetic assessment, counseling, and planning when anomalies are detected.
A personalized approach
There has been growing interest in recent years in CMA for the prenatal genetic workup of CHDs. Microarray targets chromosomal regions at a much higher resolution than traditional karyotype. Traditional karyotype assesses both changes in chromosome number as well as more subtle structural changes such as chromosomal deletions and duplications. CMA finds what traditional karyotype identifies, but in addition, it identifies much smaller, clinically relevant chromosomal deletions and duplications that are not detected by karyotype performed with or without fluorescence in-situ hybridization (FISH). FISH uses DNA probes that carry fluorescent tags to detect chromosomal DNA.
At our center, we studied the prenatal genetic test results of 145 fetuses diagnosed with CHDs. Each case involved FISH for aneuploidy/karyotype, followed by CMA in cases of a negative karyotype result. CMA increased the diagnostic yield in cases of CHD by 19.8% overall – 17.4% in cases of isolated CHD and 24.5% in cases of CHD plus extracardiac anomalies.4
Indeed, although a microarray costs more and takes an additional 2 weeks to run, CMA should be strongly considered as first-line testing for the prenatal genetic evaluation of fetuses with major structural cardiac abnormalities detected by ultrasound. However, there still are cases in which a karyotype might be sufficient. For instance, if I see that a fetus has an atrial-ventricular septal defect on a prenatal ultrasound, and there are markers for trisomy 21, 13, or 18, or Turner’s syndrome (45 XO), I usually recommend a karyotype or FISH rather than an initial CMA. If the karyotype is abnormal – which is likely in such a scenario – there isn’t a need for more extensive testing.
Similarly, when there is high suspicion for DiGeorge syndrome (the 22q11.2 deletion, which often includes cleft palate and aortic arch abnormalities), usually it is most appropriate to perform a FISH test.
CMA is the preferred first modality, however, when prenatal imaging suggests severe CHD – for instance, when there are signs of hypoplastic left heart syndrome or tetralogy of Fallot (a conotruncal defect) – or complex CHD with extracardiac anomalies. In these cases, there is a high likelihood of detecting a small deletion or duplication that would be missed with karyotype.
In the past decade, karyotype and CMA have become the major methods used in our practice. However, targeted next‐generation sequencing and whole‐exome sequencing may become more widely used because these technologies enable rapid analysis of a large number of gene sequences and facilitate discovery of novel causative genes in many genetic diseases that cause CHDs.
Currently, targeted next-generation sequencing has mainly been used in the postnatal setting, and there are limited data available on its prenatal use. Compared with whole-exome sequencing, which sequences all of the protein-coding regions of the genome, targeted next-generation sequencing panels select regions of genes that are known to be associated with diseases of interest.
For CHDs, some perinatal centers have begun using a customized gene panel that targets 77 CHD-associated genes. This particular panel has been shown to be useful in addition to current methods and is an effective tool for prenatal genetic diagnosis.5
Whole-exome sequencing is currently expensive and time consuming. While sometimes it is used in the postnatal context, it is not yet part of routine practice as a prenatal diagnostic tool. As technology advances this will change – early in the next decade, I believe. For now, whole-exome sequencing may be an option for some patients who want to know more when severe CHD is evident on ultrasound and there are negative results from CMA or targeted sequencing. We have diagnosed some rare genetic syndromes using whole-exome sequencing; these diagnoses helped us to better manage the pregnancies.
These choices are part of the case-specific, stepwise approach to genetic evaluation that we take in our fetal heart program. Our goal is to pursue information that will be accurate and valuable for the patient and clinicians, in the most cost-effective and timely manner.
Limitations of noninvasive screening
In our fetal heart program we see increasing numbers of referred patients who have chosen noninvasive cell-free fetal DNA screening (cfDNA) after a cardiac anomaly is detected on ultrasound examination, and who believe that their “low risk” results demonstrate very little or no risk of CHD. Many of these patients express a belief that noninvasive testing is highly sensitive and accurate for fetal anomalies, including CHDs, and are not easily convinced of the value of other genetic tests.
We recently conducted a retrospective chart analysis (unpublished) in which we found that 41% of cases of CHD with abnormal genetics results were not detectable by cfDNA screening.
In the case of atrial-ventricular septal defects and conotruncal abnormalities that often are more associated with common aneuploidies (trisomy 21, 18, 13, and 45 XO), a “high-risk” result from cfDNA screening may offer the family and cardiology/neonatal team some guidance, but a “low-risk” result does not eliminate the risk of a microarray abnormality and thus may provide false reassurance.
Other research has shown that noninvasive screening will miss up to 7.3% of karyotype abnormalities in pregnancies at high risk for common aneuploidies.6
While invasive testing poses a very small risk of miscarriage, it is hard without such testing to elucidate the potential genetic etiologies of CHDs and truly understand the problems. We must take time to thoughtfully counsel patients who decline invasive testing about the limitations of cfDNA screening for CHDs and other anomalies.
Dr. Turan is an associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. Dr. Turan reported that she has no disclosures relevant to this Master Class. Email her at obnews@mdedge.com.
References
1. J Am Coll Cardiol. 1988 Oct;12(4):1079-86.
2. Pediatr Cardiol. 2019 Mar;40(3):489-96.
3. Ann Pediatr Cardiol. 2017 May-Aug;10(2):126-30.
4. Eur J Obstet Gynecol Reprod Biol 2018;221:172-76.
5. Ultrasound Obstet Gynecol. 2018 Aug;52(2):205-11.
6. PLoS One. 2016 Jan 15;11(1):e0146794.
Congenital heart defects (CHDs) are etiologically heterogeneous, but in recent years it has become clear that genetics plays a larger role in the development of CHDs than was previously thought. Research has been shifting from a focus on risk – estimating the magnitude of increased risk, for instance, based on maternal or familial risk factors – to a focus on the etiology of cardiac defects.
In practice, advances in genetic testing technologies have made the underlying causes of CHDs increasingly detectable. Chromosomal microarray analysis (CMA) – technology that detects significantly more and smaller changes in the amount of chromosomal material than traditional karyotype – has been proven to increase the diagnostic yield in cases of isolated CHDs and CHDs with extracardiac anomalies. Targeted next-generation sequencing also is now available as an additional approach in selective cases, and a clinically viable option for whole-exome sequencing is fast approaching.
For researchers, genetic evaluation carries the potential to unravel remaining mysteries about underlying causes of CHDs – to provide pathological insights and identify potential therapeutic targets. Currently, about 6 % of the total pie of presumed genetic determinants of CHDs is attributed to chromosomal anomalies, 10% to copy number variants, and 12% to single-gene defects. The remaining 72% of etiology, approximately, is undetermined.
As Helen Taussig, MD, (known as the founder of pediatric cardiology) once said, common cardiac malformations occurring in otherwise “normal” individuals “must be genetic in origin.”1 Greater use of genetic testing – and in particular, of whole-exome sequencing – will drive down this “undetermined” piece of the genetics pie.
For clinicians and patients, prenatal genetic evaluation can inform clinical management, guiding decisions on the mode, timing, and location of delivery. Genetic assessments help guide the neonatal health care team in taking optimal care of the infant, and the surgeon in preparing for neonatal surgeries and postsurgical complications.
In a recent analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database, prenatal diagnosis was associated with a lower overall prevalence of major preoperative risk factors for cardiac surgery.2 Surgical outcomes themselves also have been shown to be better after the prenatal diagnosis of complex CHDs, mainly because of improvements in perioperative care.3
When genetic etiology is elucidated, the cardiologist also is better able to counsel patients about anticipated challenges – such as the propensity, with certain genetic variants of CHD, to develop neurodevelopmental delays or other cardiac complications – and to target patient follow-up. Patients also can make informed decisions about termination or continuation of a current pregnancy and about family planning in the future.
Fortunately, advances in genetics technology have paralleled technological advancements in ultrasound. As I discussed in part one of this two-part Master Class series, it is now possible to detect many major CHDs well before 16 weeks’ gestation. Checking the structure of the fetal heart at the first-trimester screening and sonography (11-14 weeks of gestation) offers the opportunity for early genetic assessment, counseling, and planning when anomalies are detected.
A personalized approach
There has been growing interest in recent years in CMA for the prenatal genetic workup of CHDs. Microarray targets chromosomal regions at a much higher resolution than traditional karyotype. Traditional karyotype assesses both changes in chromosome number as well as more subtle structural changes such as chromosomal deletions and duplications. CMA finds what traditional karyotype identifies, but in addition, it identifies much smaller, clinically relevant chromosomal deletions and duplications that are not detected by karyotype performed with or without fluorescence in-situ hybridization (FISH). FISH uses DNA probes that carry fluorescent tags to detect chromosomal DNA.
At our center, we studied the prenatal genetic test results of 145 fetuses diagnosed with CHDs. Each case involved FISH for aneuploidy/karyotype, followed by CMA in cases of a negative karyotype result. CMA increased the diagnostic yield in cases of CHD by 19.8% overall – 17.4% in cases of isolated CHD and 24.5% in cases of CHD plus extracardiac anomalies.4
Indeed, although a microarray costs more and takes an additional 2 weeks to run, CMA should be strongly considered as first-line testing for the prenatal genetic evaluation of fetuses with major structural cardiac abnormalities detected by ultrasound. However, there still are cases in which a karyotype might be sufficient. For instance, if I see that a fetus has an atrial-ventricular septal defect on a prenatal ultrasound, and there are markers for trisomy 21, 13, or 18, or Turner’s syndrome (45 XO), I usually recommend a karyotype or FISH rather than an initial CMA. If the karyotype is abnormal – which is likely in such a scenario – there isn’t a need for more extensive testing.
Similarly, when there is high suspicion for DiGeorge syndrome (the 22q11.2 deletion, which often includes cleft palate and aortic arch abnormalities), usually it is most appropriate to perform a FISH test.
CMA is the preferred first modality, however, when prenatal imaging suggests severe CHD – for instance, when there are signs of hypoplastic left heart syndrome or tetralogy of Fallot (a conotruncal defect) – or complex CHD with extracardiac anomalies. In these cases, there is a high likelihood of detecting a small deletion or duplication that would be missed with karyotype.
In the past decade, karyotype and CMA have become the major methods used in our practice. However, targeted next‐generation sequencing and whole‐exome sequencing may become more widely used because these technologies enable rapid analysis of a large number of gene sequences and facilitate discovery of novel causative genes in many genetic diseases that cause CHDs.
Currently, targeted next-generation sequencing has mainly been used in the postnatal setting, and there are limited data available on its prenatal use. Compared with whole-exome sequencing, which sequences all of the protein-coding regions of the genome, targeted next-generation sequencing panels select regions of genes that are known to be associated with diseases of interest.
For CHDs, some perinatal centers have begun using a customized gene panel that targets 77 CHD-associated genes. This particular panel has been shown to be useful in addition to current methods and is an effective tool for prenatal genetic diagnosis.5
Whole-exome sequencing is currently expensive and time consuming. While sometimes it is used in the postnatal context, it is not yet part of routine practice as a prenatal diagnostic tool. As technology advances this will change – early in the next decade, I believe. For now, whole-exome sequencing may be an option for some patients who want to know more when severe CHD is evident on ultrasound and there are negative results from CMA or targeted sequencing. We have diagnosed some rare genetic syndromes using whole-exome sequencing; these diagnoses helped us to better manage the pregnancies.
These choices are part of the case-specific, stepwise approach to genetic evaluation that we take in our fetal heart program. Our goal is to pursue information that will be accurate and valuable for the patient and clinicians, in the most cost-effective and timely manner.
Limitations of noninvasive screening
In our fetal heart program we see increasing numbers of referred patients who have chosen noninvasive cell-free fetal DNA screening (cfDNA) after a cardiac anomaly is detected on ultrasound examination, and who believe that their “low risk” results demonstrate very little or no risk of CHD. Many of these patients express a belief that noninvasive testing is highly sensitive and accurate for fetal anomalies, including CHDs, and are not easily convinced of the value of other genetic tests.
We recently conducted a retrospective chart analysis (unpublished) in which we found that 41% of cases of CHD with abnormal genetics results were not detectable by cfDNA screening.
In the case of atrial-ventricular septal defects and conotruncal abnormalities that often are more associated with common aneuploidies (trisomy 21, 18, 13, and 45 XO), a “high-risk” result from cfDNA screening may offer the family and cardiology/neonatal team some guidance, but a “low-risk” result does not eliminate the risk of a microarray abnormality and thus may provide false reassurance.
Other research has shown that noninvasive screening will miss up to 7.3% of karyotype abnormalities in pregnancies at high risk for common aneuploidies.6
While invasive testing poses a very small risk of miscarriage, it is hard without such testing to elucidate the potential genetic etiologies of CHDs and truly understand the problems. We must take time to thoughtfully counsel patients who decline invasive testing about the limitations of cfDNA screening for CHDs and other anomalies.
Dr. Turan is an associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. Dr. Turan reported that she has no disclosures relevant to this Master Class. Email her at obnews@mdedge.com.
References
1. J Am Coll Cardiol. 1988 Oct;12(4):1079-86.
2. Pediatr Cardiol. 2019 Mar;40(3):489-96.
3. Ann Pediatr Cardiol. 2017 May-Aug;10(2):126-30.
4. Eur J Obstet Gynecol Reprod Biol 2018;221:172-76.
5. Ultrasound Obstet Gynecol. 2018 Aug;52(2):205-11.
6. PLoS One. 2016 Jan 15;11(1):e0146794.
Congenital heart defects (CHDs) are etiologically heterogeneous, but in recent years it has become clear that genetics plays a larger role in the development of CHDs than was previously thought. Research has been shifting from a focus on risk – estimating the magnitude of increased risk, for instance, based on maternal or familial risk factors – to a focus on the etiology of cardiac defects.
In practice, advances in genetic testing technologies have made the underlying causes of CHDs increasingly detectable. Chromosomal microarray analysis (CMA) – technology that detects significantly more and smaller changes in the amount of chromosomal material than traditional karyotype – has been proven to increase the diagnostic yield in cases of isolated CHDs and CHDs with extracardiac anomalies. Targeted next-generation sequencing also is now available as an additional approach in selective cases, and a clinically viable option for whole-exome sequencing is fast approaching.
For researchers, genetic evaluation carries the potential to unravel remaining mysteries about underlying causes of CHDs – to provide pathological insights and identify potential therapeutic targets. Currently, about 6 % of the total pie of presumed genetic determinants of CHDs is attributed to chromosomal anomalies, 10% to copy number variants, and 12% to single-gene defects. The remaining 72% of etiology, approximately, is undetermined.
As Helen Taussig, MD, (known as the founder of pediatric cardiology) once said, common cardiac malformations occurring in otherwise “normal” individuals “must be genetic in origin.”1 Greater use of genetic testing – and in particular, of whole-exome sequencing – will drive down this “undetermined” piece of the genetics pie.
For clinicians and patients, prenatal genetic evaluation can inform clinical management, guiding decisions on the mode, timing, and location of delivery. Genetic assessments help guide the neonatal health care team in taking optimal care of the infant, and the surgeon in preparing for neonatal surgeries and postsurgical complications.
In a recent analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database, prenatal diagnosis was associated with a lower overall prevalence of major preoperative risk factors for cardiac surgery.2 Surgical outcomes themselves also have been shown to be better after the prenatal diagnosis of complex CHDs, mainly because of improvements in perioperative care.3
When genetic etiology is elucidated, the cardiologist also is better able to counsel patients about anticipated challenges – such as the propensity, with certain genetic variants of CHD, to develop neurodevelopmental delays or other cardiac complications – and to target patient follow-up. Patients also can make informed decisions about termination or continuation of a current pregnancy and about family planning in the future.
Fortunately, advances in genetics technology have paralleled technological advancements in ultrasound. As I discussed in part one of this two-part Master Class series, it is now possible to detect many major CHDs well before 16 weeks’ gestation. Checking the structure of the fetal heart at the first-trimester screening and sonography (11-14 weeks of gestation) offers the opportunity for early genetic assessment, counseling, and planning when anomalies are detected.
A personalized approach
There has been growing interest in recent years in CMA for the prenatal genetic workup of CHDs. Microarray targets chromosomal regions at a much higher resolution than traditional karyotype. Traditional karyotype assesses both changes in chromosome number as well as more subtle structural changes such as chromosomal deletions and duplications. CMA finds what traditional karyotype identifies, but in addition, it identifies much smaller, clinically relevant chromosomal deletions and duplications that are not detected by karyotype performed with or without fluorescence in-situ hybridization (FISH). FISH uses DNA probes that carry fluorescent tags to detect chromosomal DNA.
At our center, we studied the prenatal genetic test results of 145 fetuses diagnosed with CHDs. Each case involved FISH for aneuploidy/karyotype, followed by CMA in cases of a negative karyotype result. CMA increased the diagnostic yield in cases of CHD by 19.8% overall – 17.4% in cases of isolated CHD and 24.5% in cases of CHD plus extracardiac anomalies.4
Indeed, although a microarray costs more and takes an additional 2 weeks to run, CMA should be strongly considered as first-line testing for the prenatal genetic evaluation of fetuses with major structural cardiac abnormalities detected by ultrasound. However, there still are cases in which a karyotype might be sufficient. For instance, if I see that a fetus has an atrial-ventricular septal defect on a prenatal ultrasound, and there are markers for trisomy 21, 13, or 18, or Turner’s syndrome (45 XO), I usually recommend a karyotype or FISH rather than an initial CMA. If the karyotype is abnormal – which is likely in such a scenario – there isn’t a need for more extensive testing.
Similarly, when there is high suspicion for DiGeorge syndrome (the 22q11.2 deletion, which often includes cleft palate and aortic arch abnormalities), usually it is most appropriate to perform a FISH test.
CMA is the preferred first modality, however, when prenatal imaging suggests severe CHD – for instance, when there are signs of hypoplastic left heart syndrome or tetralogy of Fallot (a conotruncal defect) – or complex CHD with extracardiac anomalies. In these cases, there is a high likelihood of detecting a small deletion or duplication that would be missed with karyotype.
In the past decade, karyotype and CMA have become the major methods used in our practice. However, targeted next‐generation sequencing and whole‐exome sequencing may become more widely used because these technologies enable rapid analysis of a large number of gene sequences and facilitate discovery of novel causative genes in many genetic diseases that cause CHDs.
Currently, targeted next-generation sequencing has mainly been used in the postnatal setting, and there are limited data available on its prenatal use. Compared with whole-exome sequencing, which sequences all of the protein-coding regions of the genome, targeted next-generation sequencing panels select regions of genes that are known to be associated with diseases of interest.
For CHDs, some perinatal centers have begun using a customized gene panel that targets 77 CHD-associated genes. This particular panel has been shown to be useful in addition to current methods and is an effective tool for prenatal genetic diagnosis.5
Whole-exome sequencing is currently expensive and time consuming. While sometimes it is used in the postnatal context, it is not yet part of routine practice as a prenatal diagnostic tool. As technology advances this will change – early in the next decade, I believe. For now, whole-exome sequencing may be an option for some patients who want to know more when severe CHD is evident on ultrasound and there are negative results from CMA or targeted sequencing. We have diagnosed some rare genetic syndromes using whole-exome sequencing; these diagnoses helped us to better manage the pregnancies.
These choices are part of the case-specific, stepwise approach to genetic evaluation that we take in our fetal heart program. Our goal is to pursue information that will be accurate and valuable for the patient and clinicians, in the most cost-effective and timely manner.
Limitations of noninvasive screening
In our fetal heart program we see increasing numbers of referred patients who have chosen noninvasive cell-free fetal DNA screening (cfDNA) after a cardiac anomaly is detected on ultrasound examination, and who believe that their “low risk” results demonstrate very little or no risk of CHD. Many of these patients express a belief that noninvasive testing is highly sensitive and accurate for fetal anomalies, including CHDs, and are not easily convinced of the value of other genetic tests.
We recently conducted a retrospective chart analysis (unpublished) in which we found that 41% of cases of CHD with abnormal genetics results were not detectable by cfDNA screening.
In the case of atrial-ventricular septal defects and conotruncal abnormalities that often are more associated with common aneuploidies (trisomy 21, 18, 13, and 45 XO), a “high-risk” result from cfDNA screening may offer the family and cardiology/neonatal team some guidance, but a “low-risk” result does not eliminate the risk of a microarray abnormality and thus may provide false reassurance.
Other research has shown that noninvasive screening will miss up to 7.3% of karyotype abnormalities in pregnancies at high risk for common aneuploidies.6
While invasive testing poses a very small risk of miscarriage, it is hard without such testing to elucidate the potential genetic etiologies of CHDs and truly understand the problems. We must take time to thoughtfully counsel patients who decline invasive testing about the limitations of cfDNA screening for CHDs and other anomalies.
Dr. Turan is an associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland School of Medicine and director of the Fetal Heart Program at the University of Maryland Medical Center. Dr. Turan reported that she has no disclosures relevant to this Master Class. Email her at obnews@mdedge.com.
References
1. J Am Coll Cardiol. 1988 Oct;12(4):1079-86.
2. Pediatr Cardiol. 2019 Mar;40(3):489-96.
3. Ann Pediatr Cardiol. 2017 May-Aug;10(2):126-30.
4. Eur J Obstet Gynecol Reprod Biol 2018;221:172-76.
5. Ultrasound Obstet Gynecol. 2018 Aug;52(2):205-11.
6. PLoS One. 2016 Jan 15;11(1):e0146794.
Zulresso: Hope and lingering questions
The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).
In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).
Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABAA receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.
There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.
Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.
Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.
What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.
So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.
Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.
Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.
Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at admin@womensmentalhealth.org.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).
In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).
Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABAA receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.
There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.
Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.
Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.
What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.
So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.
Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.
Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.
Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at admin@womensmentalhealth.org.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).
In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).
Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABAA receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.
There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.
Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.
Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.
What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.
So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.
Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.
Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.
Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at admin@womensmentalhealth.org.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
Rules of incivility
Some people are civil; others are not. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.
********
Charlie is 18. His mother is with him.
“I see my colleague prescribed an antibiotic for your acne.”
“No. I stopped the medicine after 2 weeks. It’s not acne.”
“Then what do you think it is?”
“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”
“Prednisone? That is not a good treatment for acne.”
“It’s not acne.”
“If that’s how you feel, then I think you will need to get another opinion.”
“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”
(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)
“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”
“Actually, no.”
“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.
“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.
Later that day Charlie calls back. He asks my secretary where he can post a bad review.
“Try our website,” suggests my staffer.
********
Gwen has many moles. Two were severely dysplastic and required re-excision.
“There is one mole on your back that I think needs to be tested.”
“Why?”
“Because it shows irregularity at the border.”
“I really hate surgery.”
“You may not need more surgery. We should find out, though.”
“I’m not saying you’re doing this just to get more money.”
“Well, thank you for that.”
“I’m not trying to be difficult.”
(But you are succeeding, aren’t you?)
“I also have warts on my finger.”
“I can freeze those for you.”
“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”
“Thank you. I will try to do it correctly.”
“I just want to advocate for myself.”
********
“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”
“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”
“Are all of you incompetent there? I told you my name, didn’t I?”
“Just once more, if you wouldn’t mind.”
“It’s Jomes, J-O-M-E-S. Have you got that?”
“Why, yes, and thank you for your patience. Your appointment is at 1:30.”
“It may rain.”
“Yes, so they say.”
“Well?”
“I’m sorry?”
“I asked you a question.”
“What question?”
“I asked you if it is going to rain.”
“I’m sorry Mr. Jomes. I just book appointments.”
Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.
But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.
I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”
Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.
Some people are civil; others are not. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.
********
Charlie is 18. His mother is with him.
“I see my colleague prescribed an antibiotic for your acne.”
“No. I stopped the medicine after 2 weeks. It’s not acne.”
“Then what do you think it is?”
“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”
“Prednisone? That is not a good treatment for acne.”
“It’s not acne.”
“If that’s how you feel, then I think you will need to get another opinion.”
“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”
(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)
“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”
“Actually, no.”
“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.
“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.
Later that day Charlie calls back. He asks my secretary where he can post a bad review.
“Try our website,” suggests my staffer.
********
Gwen has many moles. Two were severely dysplastic and required re-excision.
“There is one mole on your back that I think needs to be tested.”
“Why?”
“Because it shows irregularity at the border.”
“I really hate surgery.”
“You may not need more surgery. We should find out, though.”
“I’m not saying you’re doing this just to get more money.”
“Well, thank you for that.”
“I’m not trying to be difficult.”
(But you are succeeding, aren’t you?)
“I also have warts on my finger.”
“I can freeze those for you.”
“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”
“Thank you. I will try to do it correctly.”
“I just want to advocate for myself.”
********
“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”
“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”
“Are all of you incompetent there? I told you my name, didn’t I?”
“Just once more, if you wouldn’t mind.”
“It’s Jomes, J-O-M-E-S. Have you got that?”
“Why, yes, and thank you for your patience. Your appointment is at 1:30.”
“It may rain.”
“Yes, so they say.”
“Well?”
“I’m sorry?”
“I asked you a question.”
“What question?”
“I asked you if it is going to rain.”
“I’m sorry Mr. Jomes. I just book appointments.”
Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.
But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.
I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”
Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.
Some people are civil; others are not. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.
********
Charlie is 18. His mother is with him.
“I see my colleague prescribed an antibiotic for your acne.”
“No. I stopped the medicine after 2 weeks. It’s not acne.”
“Then what do you think it is?”
“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”
“Prednisone? That is not a good treatment for acne.”
“It’s not acne.”
“If that’s how you feel, then I think you will need to get another opinion.”
“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”
(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)
“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”
“Actually, no.”
“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.
“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.
Later that day Charlie calls back. He asks my secretary where he can post a bad review.
“Try our website,” suggests my staffer.
********
Gwen has many moles. Two were severely dysplastic and required re-excision.
“There is one mole on your back that I think needs to be tested.”
“Why?”
“Because it shows irregularity at the border.”
“I really hate surgery.”
“You may not need more surgery. We should find out, though.”
“I’m not saying you’re doing this just to get more money.”
“Well, thank you for that.”
“I’m not trying to be difficult.”
(But you are succeeding, aren’t you?)
“I also have warts on my finger.”
“I can freeze those for you.”
“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”
“Thank you. I will try to do it correctly.”
“I just want to advocate for myself.”
********
“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”
“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”
“Are all of you incompetent there? I told you my name, didn’t I?”
“Just once more, if you wouldn’t mind.”
“It’s Jomes, J-O-M-E-S. Have you got that?”
“Why, yes, and thank you for your patience. Your appointment is at 1:30.”
“It may rain.”
“Yes, so they say.”
“Well?”
“I’m sorry?”
“I asked you a question.”
“What question?”
“I asked you if it is going to rain.”
“I’m sorry Mr. Jomes. I just book appointments.”
Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.
But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.
I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”
Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.
Summary: Preexposure prophylaxis for the prevention of HIV infection USPSTF recommendation statement
It is estimated that there are 1.1 million people in the United States living with HIV and that 15% of those people do not know they have HIV. Although the number of new cases reported each year is decreasing, there were still 38,281 new diagnoses in 2017. New cases might be decreasing overall, but the incidence of HIV is rising in some groups including people aged 25-29 years old and American Indian/Alaska Native and Asian populations. In addition, HIV disproportionately affects men who have sex with men, black/African American populations, and Hispanic/Latino populations, according to the USPSTF statement.
Given the prevalence of HIV and rising new cases in certain groups, it is thought that preexposure prophylaxis (PrEP) is being underutilized. The CDC reported that, in 2015, 1.2 million people were candidates for PrEP, but in 2017, only 100,282 people were using PrEP. The USPSTF performed a meta-analysis of 12 RCTs comparing rates of HIV infection in groups treated with PrEP versus those treated with placebo or no treatment and found a risk ratio of 0.46 (95% confidence interval, 0.33-0.66) and absolute risk reduction of –2% (95% CI, –2.8% to –1.2%) after 4 months and 4 years.
With this epidemiologic data and the meta-analysis, the USPSTF offered the following recommendations.
Screening
In order to decrease the rates of transmission and incidence of HIV infection, we must appropriately identify those who would be good candidates for PrEP. That begins with taking a complete and thorough sexual and injection drug use history in a manner that does not make patients feel stigmatized or discriminated against. The USPSTF recommends screening for HIV infection in patients aged 15-65 years old, in younger and older patients who have increased risk factors, and all pregnant patients. PrEP is not an appropriate choice in those who have HIV because it can lead to drug resistance.
When screening for HIV and considering starting PrEP, it is recommended that clinicians also test for kidney function, hepatitis B and C, other STIs, and pregnancy. The USPSTF suggests that the following groups be considered for PrEP given the increased risk of HIV infection:
- Men who have sex with men, are sexually active, and have one of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during receptive or insertive anal sex, or infection with syphilis, gonorrhea, or chlamydia in the past 6 months.
- Heterosexual men or women who are sexually active with one or more of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during sex with a partner whose HIV status is unknown and who is at high risk, and infection with syphilis or gonorrhea in the past 6 months.
- Patients who inject drugs with one or more of the following characteristics: shared use of drug injection equipment and risk of sexual acquisition (as in the categories above).
The USPSTF also notes that those who engage in transactional sex (for money, drugs, or housing) and transgender patients are at an increased risk of HIV infection.
Treatment
The only FDA approved treatment for the prevention HIV infection is once daily oral combined tenofovir disoproxil fumarate and emtricitabine; however, some studies have found that tenofovir disproxil fumarate monotherapy is also effective. Considering these trials, the CDC has suggested that tenofovir disoproxil fumarate monotherapy can be used as an alternative for men and women at high risk and those who inject drugs.
Tenofovir disoproxil fumarate/emtricitabine can also be used in pregnant patients, however the USPSTF notes that no PrEP trials included pregnant women. Additionally, tenofovir disoproxil fumarate/emtricitabine can be used in adolescents who weigh more than 35 kg. It is unknown how much time it takes to achieve protection against HIV infection after starting PrEP, and there is no clear timeline for how long patients should be on PrEP. Patients may discontinue medication because of preference, decreased risk of HIV exposure, or side effects.
Side effects include renal adverse events (serum creatinine rise), gastrointestinal adverse events (mostly nausea), and bone loss and increased fracture risk, although none were statistically significant when PrEP and placebo groups were compared. The USPSTF’s recommendations note that the effectiveness of PrEP is dependent on medication adherence.
While PrEP is an important part of preventing HIV, it is always important to counsel patients on other ways to reduce risk. The USPSTF notes that consistent condom use reduces the risk of HIV infection by around 80% in addition to reducing the risk of other STIs. All trials studied by the USPSTF for these recommendations included counseling on behavior, adherence, and condom use.
Bottom Line
It is estimated that 1.1 million Americans are living with HIV and 15% are unaware that they are positive for HIV. Overall cases of new HIV diagnoses are down, but they are rising in some groups. Every patient should be screened for high-risk sexual behavior and drug use with a thorough history. Patients aged 15-65 years should be screened for HIV. If patients are negative for HIV, but participate in high-risk sexual behaviors and drug injection, they should be offered PrEP along with counseling on, medication adherence, condom use, and reduction of high-risk behaviors.
Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Sprogell is a second-year resident in the Family Medicine Residency Program at Abington Jefferson Health
Reference
Owens DK et al. “Preexposure prophylaxis for the prevention of HIV infection: US Preventive Services Task Force recommendation statement.” JAMA. 2019 Jun 11;321(22):2203-13.
It is estimated that there are 1.1 million people in the United States living with HIV and that 15% of those people do not know they have HIV. Although the number of new cases reported each year is decreasing, there were still 38,281 new diagnoses in 2017. New cases might be decreasing overall, but the incidence of HIV is rising in some groups including people aged 25-29 years old and American Indian/Alaska Native and Asian populations. In addition, HIV disproportionately affects men who have sex with men, black/African American populations, and Hispanic/Latino populations, according to the USPSTF statement.
Given the prevalence of HIV and rising new cases in certain groups, it is thought that preexposure prophylaxis (PrEP) is being underutilized. The CDC reported that, in 2015, 1.2 million people were candidates for PrEP, but in 2017, only 100,282 people were using PrEP. The USPSTF performed a meta-analysis of 12 RCTs comparing rates of HIV infection in groups treated with PrEP versus those treated with placebo or no treatment and found a risk ratio of 0.46 (95% confidence interval, 0.33-0.66) and absolute risk reduction of –2% (95% CI, –2.8% to –1.2%) after 4 months and 4 years.
With this epidemiologic data and the meta-analysis, the USPSTF offered the following recommendations.
Screening
In order to decrease the rates of transmission and incidence of HIV infection, we must appropriately identify those who would be good candidates for PrEP. That begins with taking a complete and thorough sexual and injection drug use history in a manner that does not make patients feel stigmatized or discriminated against. The USPSTF recommends screening for HIV infection in patients aged 15-65 years old, in younger and older patients who have increased risk factors, and all pregnant patients. PrEP is not an appropriate choice in those who have HIV because it can lead to drug resistance.
When screening for HIV and considering starting PrEP, it is recommended that clinicians also test for kidney function, hepatitis B and C, other STIs, and pregnancy. The USPSTF suggests that the following groups be considered for PrEP given the increased risk of HIV infection:
- Men who have sex with men, are sexually active, and have one of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during receptive or insertive anal sex, or infection with syphilis, gonorrhea, or chlamydia in the past 6 months.
- Heterosexual men or women who are sexually active with one or more of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during sex with a partner whose HIV status is unknown and who is at high risk, and infection with syphilis or gonorrhea in the past 6 months.
- Patients who inject drugs with one or more of the following characteristics: shared use of drug injection equipment and risk of sexual acquisition (as in the categories above).
The USPSTF also notes that those who engage in transactional sex (for money, drugs, or housing) and transgender patients are at an increased risk of HIV infection.
Treatment
The only FDA approved treatment for the prevention HIV infection is once daily oral combined tenofovir disoproxil fumarate and emtricitabine; however, some studies have found that tenofovir disproxil fumarate monotherapy is also effective. Considering these trials, the CDC has suggested that tenofovir disoproxil fumarate monotherapy can be used as an alternative for men and women at high risk and those who inject drugs.
Tenofovir disoproxil fumarate/emtricitabine can also be used in pregnant patients, however the USPSTF notes that no PrEP trials included pregnant women. Additionally, tenofovir disoproxil fumarate/emtricitabine can be used in adolescents who weigh more than 35 kg. It is unknown how much time it takes to achieve protection against HIV infection after starting PrEP, and there is no clear timeline for how long patients should be on PrEP. Patients may discontinue medication because of preference, decreased risk of HIV exposure, or side effects.
Side effects include renal adverse events (serum creatinine rise), gastrointestinal adverse events (mostly nausea), and bone loss and increased fracture risk, although none were statistically significant when PrEP and placebo groups were compared. The USPSTF’s recommendations note that the effectiveness of PrEP is dependent on medication adherence.
While PrEP is an important part of preventing HIV, it is always important to counsel patients on other ways to reduce risk. The USPSTF notes that consistent condom use reduces the risk of HIV infection by around 80% in addition to reducing the risk of other STIs. All trials studied by the USPSTF for these recommendations included counseling on behavior, adherence, and condom use.
Bottom Line
It is estimated that 1.1 million Americans are living with HIV and 15% are unaware that they are positive for HIV. Overall cases of new HIV diagnoses are down, but they are rising in some groups. Every patient should be screened for high-risk sexual behavior and drug use with a thorough history. Patients aged 15-65 years should be screened for HIV. If patients are negative for HIV, but participate in high-risk sexual behaviors and drug injection, they should be offered PrEP along with counseling on, medication adherence, condom use, and reduction of high-risk behaviors.
Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Sprogell is a second-year resident in the Family Medicine Residency Program at Abington Jefferson Health
Reference
Owens DK et al. “Preexposure prophylaxis for the prevention of HIV infection: US Preventive Services Task Force recommendation statement.” JAMA. 2019 Jun 11;321(22):2203-13.
It is estimated that there are 1.1 million people in the United States living with HIV and that 15% of those people do not know they have HIV. Although the number of new cases reported each year is decreasing, there were still 38,281 new diagnoses in 2017. New cases might be decreasing overall, but the incidence of HIV is rising in some groups including people aged 25-29 years old and American Indian/Alaska Native and Asian populations. In addition, HIV disproportionately affects men who have sex with men, black/African American populations, and Hispanic/Latino populations, according to the USPSTF statement.
Given the prevalence of HIV and rising new cases in certain groups, it is thought that preexposure prophylaxis (PrEP) is being underutilized. The CDC reported that, in 2015, 1.2 million people were candidates for PrEP, but in 2017, only 100,282 people were using PrEP. The USPSTF performed a meta-analysis of 12 RCTs comparing rates of HIV infection in groups treated with PrEP versus those treated with placebo or no treatment and found a risk ratio of 0.46 (95% confidence interval, 0.33-0.66) and absolute risk reduction of –2% (95% CI, –2.8% to –1.2%) after 4 months and 4 years.
With this epidemiologic data and the meta-analysis, the USPSTF offered the following recommendations.
Screening
In order to decrease the rates of transmission and incidence of HIV infection, we must appropriately identify those who would be good candidates for PrEP. That begins with taking a complete and thorough sexual and injection drug use history in a manner that does not make patients feel stigmatized or discriminated against. The USPSTF recommends screening for HIV infection in patients aged 15-65 years old, in younger and older patients who have increased risk factors, and all pregnant patients. PrEP is not an appropriate choice in those who have HIV because it can lead to drug resistance.
When screening for HIV and considering starting PrEP, it is recommended that clinicians also test for kidney function, hepatitis B and C, other STIs, and pregnancy. The USPSTF suggests that the following groups be considered for PrEP given the increased risk of HIV infection:
- Men who have sex with men, are sexually active, and have one of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during receptive or insertive anal sex, or infection with syphilis, gonorrhea, or chlamydia in the past 6 months.
- Heterosexual men or women who are sexually active with one or more of these additional characteristics: a serodiscordant sex partner, inconsistent use of condoms during sex with a partner whose HIV status is unknown and who is at high risk, and infection with syphilis or gonorrhea in the past 6 months.
- Patients who inject drugs with one or more of the following characteristics: shared use of drug injection equipment and risk of sexual acquisition (as in the categories above).
The USPSTF also notes that those who engage in transactional sex (for money, drugs, or housing) and transgender patients are at an increased risk of HIV infection.
Treatment
The only FDA approved treatment for the prevention HIV infection is once daily oral combined tenofovir disoproxil fumarate and emtricitabine; however, some studies have found that tenofovir disproxil fumarate monotherapy is also effective. Considering these trials, the CDC has suggested that tenofovir disoproxil fumarate monotherapy can be used as an alternative for men and women at high risk and those who inject drugs.
Tenofovir disoproxil fumarate/emtricitabine can also be used in pregnant patients, however the USPSTF notes that no PrEP trials included pregnant women. Additionally, tenofovir disoproxil fumarate/emtricitabine can be used in adolescents who weigh more than 35 kg. It is unknown how much time it takes to achieve protection against HIV infection after starting PrEP, and there is no clear timeline for how long patients should be on PrEP. Patients may discontinue medication because of preference, decreased risk of HIV exposure, or side effects.
Side effects include renal adverse events (serum creatinine rise), gastrointestinal adverse events (mostly nausea), and bone loss and increased fracture risk, although none were statistically significant when PrEP and placebo groups were compared. The USPSTF’s recommendations note that the effectiveness of PrEP is dependent on medication adherence.
While PrEP is an important part of preventing HIV, it is always important to counsel patients on other ways to reduce risk. The USPSTF notes that consistent condom use reduces the risk of HIV infection by around 80% in addition to reducing the risk of other STIs. All trials studied by the USPSTF for these recommendations included counseling on behavior, adherence, and condom use.
Bottom Line
It is estimated that 1.1 million Americans are living with HIV and 15% are unaware that they are positive for HIV. Overall cases of new HIV diagnoses are down, but they are rising in some groups. Every patient should be screened for high-risk sexual behavior and drug use with a thorough history. Patients aged 15-65 years should be screened for HIV. If patients are negative for HIV, but participate in high-risk sexual behaviors and drug injection, they should be offered PrEP along with counseling on, medication adherence, condom use, and reduction of high-risk behaviors.
Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Sprogell is a second-year resident in the Family Medicine Residency Program at Abington Jefferson Health
Reference
Owens DK et al. “Preexposure prophylaxis for the prevention of HIV infection: US Preventive Services Task Force recommendation statement.” JAMA. 2019 Jun 11;321(22):2203-13.