Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with hyperandrogenism and is caused by occlusion or rupture of follicular units and inflammation of the apocrine glands.^1-3 The disease most commonly affects women (female to male ratio of 3:1) of childbearing age.^1,2,4,5 Body areas affected include the axillae and groin, and less commonly the perineum; perianal region; and skin folds, such as gluteal, inframammary, and infraumbilical folds.^1,2 Symptoms manifest as painful subcutaneous nodules with possible accompanying purulent drainage, sinus tracts, and/or dermal contractures. Although the pathophysiology is unclear, androgens affect the course of HS during pregnancy by stimulating the affected glands and altering cytokines.^1,2,6

During pregnancy, maternal immune function switches from cell-mediated T helper cell (T_H1) to humoral T_H2 cytokine production. The activity of sebaceous and eccrine glands increases while the activity of apocrine glands decreases, thus changing the inflammatory course of HS during pregnancy.³ Approximately 20% of women with HS experience improvement of symptoms during pregnancy, while the remainder either experience no relief or deterioration of symptoms.¹ Improvement in symptoms during pregnancy was found to occur more frequently in those who had worsening symptoms during menses owing to the possible hormonal effect estrogen has on inhibiting T_H1 and T_H17 proinflammatory cytokines, which promotes an immunosuppressive environment.⁴

Lactation and breastfeeding abilities may be hindered if a woman has HS affecting the apocrine glands of breast tissue and a symptom flare in the postpartum period. If HS causes notable inflammation in the nipple-areolar complex during pregnancy, the patient may experience difficulties with lactation and milk fistula formation, leading to inability to breastfeed.² Another reason why mothers with HS may not be able to breastfeed is that the medications required to treat the disease are unsafe if passed to the infant via breast milk. In addition, the teratogenic effects of HS medications may necessitate therapy adjustments in pregnancy.¹ Here, we provide a brief overview of the medical management considerations of HS in the setting of pregnancy and the impact on breastfeeding.

MEDICAL MANAGEMENT AND DRUG SAFETY

Dermatologists prescribe a myriad of topical and systemic medications to ameliorate symptoms of HS. Therapy regimens often are multimodal and include antibiotics, biologics, and immunosuppressants.^1,3

Antibiotics

First-line antibiotics include clindamycin, metronidazole, tetracyclines, erythromycin, rifampin, dapsone, and fluoroquinolones. Topical clindamycin 1%, metronidazole 0.75%, and erythromycin 2% are used for open or active HS lesions and are all safe to use in pregnancy since there is minimal systemic absorption and minimal excretion into breast milk.¹ Topical antimicrobial washes such as benzoyl peroxide and chlorhexidine often are used in combination with systemic medications to treat HS. These washes are safe during pregnancy and lactation, as they have minimal systemic absorption.⁷

Of these first-line antibiotics, only tetracyclines are contraindicated during pregnancy and lactation, as they are deemed to be in category D by the US Food and Drug Administration (FDA).¹ Aside from tetracyclines, these antibiotics do not cause birth defects and are safe for nursing infants.^1,8 Systemic clindamycin is safe during pregnancy and breastfeeding. Systemic metronidazole also is safe for use in pregnant patients but needs to be discontinued 12 to 24 hours prior to breastfeeding, which often prohibits appropriate dosing.¹

Systemic Erythromycin—There are several forms of systemic erythromycin, including erythromycin base, erythromycin estolate, erythromycin ethylsuccinate (EES), and erythromycin stearate. Erythromycin estolate is contraindicated in pregnancy because it is associated with reversible maternal hepatoxicity and jaundice.^9-11 Erythromycin ethylsuccinate is the preferred form for pregnant patients. Providers should exercise caution when prescribing EES to lactating mothers, as small amounts are still secreted through breast milk.¹¹ Some studies have shown an increased risk for development of infantile hypertrophic pyloric stenosis with systemic erythromycin use, especially if a neonate is exposed in the first 14 days of life. Thus, we recommend withholding EES for 2 weeks after delivery if the patient is breastfeeding. A follow-up study did not find any association between erythromycin and infantile hypertrophic pyloric stenosis; however, the American Academy of Pediatrics still recommends short-term use only of erythromycin if it is to be used in the systemic form.⁸

Rifampin—Rifampin is excreted into breast milk but without adverse effects to the infant. Rifampin also is safe in pregnancy but should be used on a case-by-case basis in pregnant or nursing women because it is a cytochrome P450 inducer.

Dapsone—Dapsone has no increased risk for congenital anomalies. However, it is associated with hemolytic anemia and neonatal hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.¹² Newborns exposed to dapsone are at an increased risk for methemoglobinemia owing to increased sensitivity of fetal erythrocytes to oxidizing agents.¹³ If dapsone use is necessary, stopping dapsone treatment in the last month of gestation is recommended to minimize risk for kernicterus.⁹ Dapsone can be found in high concentrations in breast milk at 14.3% of the maternal dose. It is still safe to use during breastfeeding, but there is a risk of the infant developing hyperbilirubinemia/G6PD deficiency.^1,8 Thus, physicians may consider performing a G6PD screen on infants to determine if breastfeeding is safe.¹²

Fluoroquinolones—Quinolones are not contraindicated during pregnancy, but they can damage fetal cartilage and thus should be reserved for use in complicated infections when the benefits outweigh the risks.¹² Quinolones are believed to increase risk for arthropathy but are safe for use in lactation. When quinolones are digested with milk, exposure decreases below pediatric doses because of the ionized property of calcium in milk.⁸

Tumor Necrosis Factor α Inhibitors—The safety of anti–tumor necrosis factor (TNF) α biologics in pregnancy is less certain when compared with antibiotics.¹ Anti–TNF-α inhibitors such as etanercept, adalimumab, and infliximab are all labeled as FDA category B, meaning there are no well-controlled human studies of the drugs.⁹ There are limited data that support safe use of TNF-α inhibitors prior to the third trimester before maternal IgG antibodies are transferred to the fetus via the placenta.^1,13 Anti–TNF-α inhibitors may be safe when breastfeeding because the drugs have large molecular weights that prevent them from entering breast milk in large amounts. Absorption also is limited due to the infant’s digestive acids and enzymes breaking down the protein structure of the medication.⁸ Overall, TNF-α inhibitor use is still controversial and only used if the benefits outweigh the risks during pregnancy or if there is no alternative treatment.^1,3,9

Ustekinumab and Anakinra—Ustekinumab (an IL-12/IL-23 inhibitor) and anakinra (an IL-1α and IL-1β inhibitor) also are FDA category B drugs and have limited data supporting their use as HS treatment in pregnancy. Anakinra may have evidence of compatibility with breastfeeding, as endogenous IL-1α inhibitor is found in colostrum and mature breast milk.¹

Immunosuppressants

Immunosuppressants that are used to treat HS include corticosteroids and cyclosporine.

Corticosteroids—Topical corticosteroids can be used safely in lactation if they are not applied directly to the nipple or any area that makes direct contact with the infant’s mouth. Intralesional corticosteroid injections are safe for use during both pregnancy and breastfeeding to decrease inflammation of acutely flaring lesions and can be considered first-line treatment.¹ Oral glucocorticoids also can be safely used for acute flares during pregnancy; however, prolonged use is associated with pregnancy complications such as preeclampsia, eclampsia, premature delivery, and gestational diabetes.¹² There also is a small risk of oral cleft deformity in the infant; thus, potent corticosteroids are recommended in short durations during pregnancy, and there are no adverse effects if the maternal dose is less than 10 mg daily.^8,12 Systemic steroids are safe to use with breastfeeding, but patients should be advised to wait 4 hours after ingesting medication before breastfeeding.^1,8

Cyclosporine—Topical and oral calcineurin inhibitors such as cyclosporine have low risk for transmission into breast milk; however, potential effects of exposure through breast milk are unknown. For that reason, manufacturers state that cyclosporine use is contraindicated during lactation.⁸ If cyclosporine is to be used by a breastfeeding woman, monitoring cyclosporine concentrations in the infant is suggested to ensure that the exposure is less than 5% to 10% of the therapeutic dose.¹³ The use of cyclosporine has been extensively studied in pregnant transplant patients and is considered relatively safe for use in pregnancy.¹⁴ Cyclosporine is lipid soluble and thus is quickly metabolized and spread throughout the body; it can easily cross the placenta.^9,13 Blood concentration in the fetus is 30% to 64% that of the maternal circulation. However, cyclosporine is only toxic to the fetus at maternally toxic doses, which can result in low birth weight and increased prenatal and postnatal mortality.¹³

Isotretinoin, Oral Contraceptive Pills, and Spironolactone

Isotretinoin and hormonal treatments such as oral contraceptive pills and spironolactone (an androgen receptor blocker) commonly are used to treat HS, but all are contraindicated in pregnancy and lactation. Isotretinoin is a well-established teratogen, but adverse effects on nursing babies have not been described. However, the manufacturer of isotretinoin advises against its use in lactation. Oral contraceptive pill use in early pregnancy is associated with increased risk for Down syndrome. Oral contraceptive pill use also is contraindicated in lactation for 2 reasons: decreased milk production and risk for fetal feminization. Antiandrogenic agents such as spironolactone have been shown to be associated with hypospadias and feminization of the male fetus.⁷

COMMENT

Women with HS usually require ongoing medical treatment during pregnancy and immediately postpartum; thus, it is important that treatments are proven to be safe for use in this specific population. Current management guidelines are not entirely suitable for pregnant and breastfeeding women given that many HS drugs have teratogenic effects and/or can be excreted into breast milk.¹ Several treatments have uncertain safety profiles in pregnancy and breastfeeding, which calls for dermatologists to change or create new regimens for their patients. Close management also is necessary to prevent excess inflammation of breast tissue and milk fistula formation, which would hinder normal breastfeeding.

The eTable lists medications used to treat HS. The FDA category is listed next to each drug. However, it should be noted that these FDA letter categories were replaced with the Pregnancy and Lactation Labeling Rule in 2015. The letter ratings were deemed overly simplistic and replaced with narrative-based labeling that provides more detailed adverse effects and clinical considerations.⁹

Risk Factors of HS—Predisposing risk factors for HS flares that are controllable include obesity and smoking.² Pregnancy weight gain may cause increased skin maceration at intertriginous sites, which can contribute to worsening HS symptoms.^1,5 Adipocytes play a role in HS exacerbation by promoting secretion of TNF-α, leading to increased inflammation.⁵ Dermatologists can help prevent postpartum HS flares by monitoring weight gain during pregnancy, encouraging smoking cessation, and promoting weight and nutrition goals as set by an obstetrician.¹ In addition to medications, management of HS should include emotional support and education on wearing loose-fitting clothing to avoid irritation of the affected areas.³ An emphasis on dermatologist counseling for all patients with HS, even for those with milder disease, can reduce exacerbations during pregnancy.⁵

CONCLUSION

The selection of dermatologic drugs for the treatment of HS in the setting of pregnancy involves complex decision-making. Dermatologists need more guidelines and proven safety data in human trials, especially regarding use of biologics and immunosuppressants to better treat HS in pregnancy. With more data, they can create more evidence-based treatment regimens to help prevent postpartum exacerbations of HS. Thus, patients can breastfeed their infants comfortably and without any risks of impaired child development. In the meantime, dermatologists can continue to work together with obstetricians and psychiatrists to decrease disease flares through counseling patients on nutrition and weight gain and providing emotional support.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with hyperandrogenism and is caused by occlusion or rupture of follicular units and inflammation of the apocrine glands.^1-3 The disease most commonly affects women (female to male ratio of 3:1) of childbearing age.^1,2,4,5 Body areas affected include the axillae and groin, and less commonly the perineum; perianal region; and skin folds, such as gluteal, inframammary, and infraumbilical folds.^1,2 Symptoms manifest as painful subcutaneous nodules with possible accompanying purulent drainage, sinus tracts, and/or dermal contractures. Although the pathophysiology is unclear, androgens affect the course of HS during pregnancy by stimulating the affected glands and altering cytokines.^1,2,6

During pregnancy, maternal immune function switches from cell-mediated T helper cell (T_H1) to humoral T_H2 cytokine production. The activity of sebaceous and eccrine glands increases while the activity of apocrine glands decreases, thus changing the inflammatory course of HS during pregnancy.³ Approximately 20% of women with HS experience improvement of symptoms during pregnancy, while the remainder either experience no relief or deterioration of symptoms.¹ Improvement in symptoms during pregnancy was found to occur more frequently in those who had worsening symptoms during menses owing to the possible hormonal effect estrogen has on inhibiting T_H1 and T_H17 proinflammatory cytokines, which promotes an immunosuppressive environment.⁴

Lactation and breastfeeding abilities may be hindered if a woman has HS affecting the apocrine glands of breast tissue and a symptom flare in the postpartum period. If HS causes notable inflammation in the nipple-areolar complex during pregnancy, the patient may experience difficulties with lactation and milk fistula formation, leading to inability to breastfeed.² Another reason why mothers with HS may not be able to breastfeed is that the medications required to treat the disease are unsafe if passed to the infant via breast milk. In addition, the teratogenic effects of HS medications may necessitate therapy adjustments in pregnancy.¹ Here, we provide a brief overview of the medical management considerations of HS in the setting of pregnancy and the impact on breastfeeding.

MEDICAL MANAGEMENT AND DRUG SAFETY

Dermatologists prescribe a myriad of topical and systemic medications to ameliorate symptoms of HS. Therapy regimens often are multimodal and include antibiotics, biologics, and immunosuppressants.^1,3

Antibiotics

First-line antibiotics include clindamycin, metronidazole, tetracyclines, erythromycin, rifampin, dapsone, and fluoroquinolones. Topical clindamycin 1%, metronidazole 0.75%, and erythromycin 2% are used for open or active HS lesions and are all safe to use in pregnancy since there is minimal systemic absorption and minimal excretion into breast milk.¹ Topical antimicrobial washes such as benzoyl peroxide and chlorhexidine often are used in combination with systemic medications to treat HS. These washes are safe during pregnancy and lactation, as they have minimal systemic absorption.⁷

Of these first-line antibiotics, only tetracyclines are contraindicated during pregnancy and lactation, as they are deemed to be in category D by the US Food and Drug Administration (FDA).¹ Aside from tetracyclines, these antibiotics do not cause birth defects and are safe for nursing infants.^1,8 Systemic clindamycin is safe during pregnancy and breastfeeding. Systemic metronidazole also is safe for use in pregnant patients but needs to be discontinued 12 to 24 hours prior to breastfeeding, which often prohibits appropriate dosing.¹

Systemic Erythromycin—There are several forms of systemic erythromycin, including erythromycin base, erythromycin estolate, erythromycin ethylsuccinate (EES), and erythromycin stearate. Erythromycin estolate is contraindicated in pregnancy because it is associated with reversible maternal hepatoxicity and jaundice.^9-11 Erythromycin ethylsuccinate is the preferred form for pregnant patients. Providers should exercise caution when prescribing EES to lactating mothers, as small amounts are still secreted through breast milk.¹¹ Some studies have shown an increased risk for development of infantile hypertrophic pyloric stenosis with systemic erythromycin use, especially if a neonate is exposed in the first 14 days of life. Thus, we recommend withholding EES for 2 weeks after delivery if the patient is breastfeeding. A follow-up study did not find any association between erythromycin and infantile hypertrophic pyloric stenosis; however, the American Academy of Pediatrics still recommends short-term use only of erythromycin if it is to be used in the systemic form.⁸

Rifampin—Rifampin is excreted into breast milk but without adverse effects to the infant. Rifampin also is safe in pregnancy but should be used on a case-by-case basis in pregnant or nursing women because it is a cytochrome P450 inducer.

Dapsone—Dapsone has no increased risk for congenital anomalies. However, it is associated with hemolytic anemia and neonatal hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.¹² Newborns exposed to dapsone are at an increased risk for methemoglobinemia owing to increased sensitivity of fetal erythrocytes to oxidizing agents.¹³ If dapsone use is necessary, stopping dapsone treatment in the last month of gestation is recommended to minimize risk for kernicterus.⁹ Dapsone can be found in high concentrations in breast milk at 14.3% of the maternal dose. It is still safe to use during breastfeeding, but there is a risk of the infant developing hyperbilirubinemia/G6PD deficiency.^1,8 Thus, physicians may consider performing a G6PD screen on infants to determine if breastfeeding is safe.¹²

Fluoroquinolones—Quinolones are not contraindicated during pregnancy, but they can damage fetal cartilage and thus should be reserved for use in complicated infections when the benefits outweigh the risks.¹² Quinolones are believed to increase risk for arthropathy but are safe for use in lactation. When quinolones are digested with milk, exposure decreases below pediatric doses because of the ionized property of calcium in milk.⁸

Tumor Necrosis Factor α Inhibitors—The safety of anti–tumor necrosis factor (TNF) α biologics in pregnancy is less certain when compared with antibiotics.¹ Anti–TNF-α inhibitors such as etanercept, adalimumab, and infliximab are all labeled as FDA category B, meaning there are no well-controlled human studies of the drugs.⁹ There are limited data that support safe use of TNF-α inhibitors prior to the third trimester before maternal IgG antibodies are transferred to the fetus via the placenta.^1,13 Anti–TNF-α inhibitors may be safe when breastfeeding because the drugs have large molecular weights that prevent them from entering breast milk in large amounts. Absorption also is limited due to the infant’s digestive acids and enzymes breaking down the protein structure of the medication.⁸ Overall, TNF-α inhibitor use is still controversial and only used if the benefits outweigh the risks during pregnancy or if there is no alternative treatment.^1,3,9

Ustekinumab and Anakinra—Ustekinumab (an IL-12/IL-23 inhibitor) and anakinra (an IL-1α and IL-1β inhibitor) also are FDA category B drugs and have limited data supporting their use as HS treatment in pregnancy. Anakinra may have evidence of compatibility with breastfeeding, as endogenous IL-1α inhibitor is found in colostrum and mature breast milk.¹

Immunosuppressants

Immunosuppressants that are used to treat HS include corticosteroids and cyclosporine.

Corticosteroids—Topical corticosteroids can be used safely in lactation if they are not applied directly to the nipple or any area that makes direct contact with the infant’s mouth. Intralesional corticosteroid injections are safe for use during both pregnancy and breastfeeding to decrease inflammation of acutely flaring lesions and can be considered first-line treatment.¹ Oral glucocorticoids also can be safely used for acute flares during pregnancy; however, prolonged use is associated with pregnancy complications such as preeclampsia, eclampsia, premature delivery, and gestational diabetes.¹² There also is a small risk of oral cleft deformity in the infant; thus, potent corticosteroids are recommended in short durations during pregnancy, and there are no adverse effects if the maternal dose is less than 10 mg daily.^8,12 Systemic steroids are safe to use with breastfeeding, but patients should be advised to wait 4 hours after ingesting medication before breastfeeding.^1,8

Cyclosporine—Topical and oral calcineurin inhibitors such as cyclosporine have low risk for transmission into breast milk; however, potential effects of exposure through breast milk are unknown. For that reason, manufacturers state that cyclosporine use is contraindicated during lactation.⁸ If cyclosporine is to be used by a breastfeeding woman, monitoring cyclosporine concentrations in the infant is suggested to ensure that the exposure is less than 5% to 10% of the therapeutic dose.¹³ The use of cyclosporine has been extensively studied in pregnant transplant patients and is considered relatively safe for use in pregnancy.¹⁴ Cyclosporine is lipid soluble and thus is quickly metabolized and spread throughout the body; it can easily cross the placenta.^9,13 Blood concentration in the fetus is 30% to 64% that of the maternal circulation. However, cyclosporine is only toxic to the fetus at maternally toxic doses, which can result in low birth weight and increased prenatal and postnatal mortality.¹³

Isotretinoin, Oral Contraceptive Pills, and Spironolactone

Isotretinoin and hormonal treatments such as oral contraceptive pills and spironolactone (an androgen receptor blocker) commonly are used to treat HS, but all are contraindicated in pregnancy and lactation. Isotretinoin is a well-established teratogen, but adverse effects on nursing babies have not been described. However, the manufacturer of isotretinoin advises against its use in lactation. Oral contraceptive pill use in early pregnancy is associated with increased risk for Down syndrome. Oral contraceptive pill use also is contraindicated in lactation for 2 reasons: decreased milk production and risk for fetal feminization. Antiandrogenic agents such as spironolactone have been shown to be associated with hypospadias and feminization of the male fetus.⁷

COMMENT

Women with HS usually require ongoing medical treatment during pregnancy and immediately postpartum; thus, it is important that treatments are proven to be safe for use in this specific population. Current management guidelines are not entirely suitable for pregnant and breastfeeding women given that many HS drugs have teratogenic effects and/or can be excreted into breast milk.¹ Several treatments have uncertain safety profiles in pregnancy and breastfeeding, which calls for dermatologists to change or create new regimens for their patients. Close management also is necessary to prevent excess inflammation of breast tissue and milk fistula formation, which would hinder normal breastfeeding.

The eTable lists medications used to treat HS. The FDA category is listed next to each drug. However, it should be noted that these FDA letter categories were replaced with the Pregnancy and Lactation Labeling Rule in 2015. The letter ratings were deemed overly simplistic and replaced with narrative-based labeling that provides more detailed adverse effects and clinical considerations.⁹

Risk Factors of HS—Predisposing risk factors for HS flares that are controllable include obesity and smoking.² Pregnancy weight gain may cause increased skin maceration at intertriginous sites, which can contribute to worsening HS symptoms.^1,5 Adipocytes play a role in HS exacerbation by promoting secretion of TNF-α, leading to increased inflammation.⁵ Dermatologists can help prevent postpartum HS flares by monitoring weight gain during pregnancy, encouraging smoking cessation, and promoting weight and nutrition goals as set by an obstetrician.¹ In addition to medications, management of HS should include emotional support and education on wearing loose-fitting clothing to avoid irritation of the affected areas.³ An emphasis on dermatologist counseling for all patients with HS, even for those with milder disease, can reduce exacerbations during pregnancy.⁵

CONCLUSION

The selection of dermatologic drugs for the treatment of HS in the setting of pregnancy involves complex decision-making. Dermatologists need more guidelines and proven safety data in human trials, especially regarding use of biologics and immunosuppressants to better treat HS in pregnancy. With more data, they can create more evidence-based treatment regimens to help prevent postpartum exacerbations of HS. Thus, patients can breastfeed their infants comfortably and without any risks of impaired child development. In the meantime, dermatologists can continue to work together with obstetricians and psychiatrists to decrease disease flares through counseling patients on nutrition and weight gain and providing emotional support.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with hyperandrogenism and is caused by occlusion or rupture of follicular units and inflammation of the apocrine glands.^1-3 The disease most commonly affects women (female to male ratio of 3:1) of childbearing age.^1,2,4,5 Body areas affected include the axillae and groin, and less commonly the perineum; perianal region; and skin folds, such as gluteal, inframammary, and infraumbilical folds.^1,2 Symptoms manifest as painful subcutaneous nodules with possible accompanying purulent drainage, sinus tracts, and/or dermal contractures. Although the pathophysiology is unclear, androgens affect the course of HS during pregnancy by stimulating the affected glands and altering cytokines.^1,2,6

During pregnancy, maternal immune function switches from cell-mediated T helper cell (T_H1) to humoral T_H2 cytokine production. The activity of sebaceous and eccrine glands increases while the activity of apocrine glands decreases, thus changing the inflammatory course of HS during pregnancy.³ Approximately 20% of women with HS experience improvement of symptoms during pregnancy, while the remainder either experience no relief or deterioration of symptoms.¹ Improvement in symptoms during pregnancy was found to occur more frequently in those who had worsening symptoms during menses owing to the possible hormonal effect estrogen has on inhibiting T_H1 and T_H17 proinflammatory cytokines, which promotes an immunosuppressive environment.⁴

Lactation and breastfeeding abilities may be hindered if a woman has HS affecting the apocrine glands of breast tissue and a symptom flare in the postpartum period. If HS causes notable inflammation in the nipple-areolar complex during pregnancy, the patient may experience difficulties with lactation and milk fistula formation, leading to inability to breastfeed.² Another reason why mothers with HS may not be able to breastfeed is that the medications required to treat the disease are unsafe if passed to the infant via breast milk. In addition, the teratogenic effects of HS medications may necessitate therapy adjustments in pregnancy.¹ Here, we provide a brief overview of the medical management considerations of HS in the setting of pregnancy and the impact on breastfeeding.

MEDICAL MANAGEMENT AND DRUG SAFETY

Dermatologists prescribe a myriad of topical and systemic medications to ameliorate symptoms of HS. Therapy regimens often are multimodal and include antibiotics, biologics, and immunosuppressants.^1,3

Antibiotics

First-line antibiotics include clindamycin, metronidazole, tetracyclines, erythromycin, rifampin, dapsone, and fluoroquinolones. Topical clindamycin 1%, metronidazole 0.75%, and erythromycin 2% are used for open or active HS lesions and are all safe to use in pregnancy since there is minimal systemic absorption and minimal excretion into breast milk.¹ Topical antimicrobial washes such as benzoyl peroxide and chlorhexidine often are used in combination with systemic medications to treat HS. These washes are safe during pregnancy and lactation, as they have minimal systemic absorption.⁷

Of these first-line antibiotics, only tetracyclines are contraindicated during pregnancy and lactation, as they are deemed to be in category D by the US Food and Drug Administration (FDA).¹ Aside from tetracyclines, these antibiotics do not cause birth defects and are safe for nursing infants.^1,8 Systemic clindamycin is safe during pregnancy and breastfeeding. Systemic metronidazole also is safe for use in pregnant patients but needs to be discontinued 12 to 24 hours prior to breastfeeding, which often prohibits appropriate dosing.¹

Systemic Erythromycin—There are several forms of systemic erythromycin, including erythromycin base, erythromycin estolate, erythromycin ethylsuccinate (EES), and erythromycin stearate. Erythromycin estolate is contraindicated in pregnancy because it is associated with reversible maternal hepatoxicity and jaundice.^9-11 Erythromycin ethylsuccinate is the preferred form for pregnant patients. Providers should exercise caution when prescribing EES to lactating mothers, as small amounts are still secreted through breast milk.¹¹ Some studies have shown an increased risk for development of infantile hypertrophic pyloric stenosis with systemic erythromycin use, especially if a neonate is exposed in the first 14 days of life. Thus, we recommend withholding EES for 2 weeks after delivery if the patient is breastfeeding. A follow-up study did not find any association between erythromycin and infantile hypertrophic pyloric stenosis; however, the American Academy of Pediatrics still recommends short-term use only of erythromycin if it is to be used in the systemic form.⁸

Rifampin—Rifampin is excreted into breast milk but without adverse effects to the infant. Rifampin also is safe in pregnancy but should be used on a case-by-case basis in pregnant or nursing women because it is a cytochrome P450 inducer.

Dapsone—Dapsone has no increased risk for congenital anomalies. However, it is associated with hemolytic anemia and neonatal hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.¹² Newborns exposed to dapsone are at an increased risk for methemoglobinemia owing to increased sensitivity of fetal erythrocytes to oxidizing agents.¹³ If dapsone use is necessary, stopping dapsone treatment in the last month of gestation is recommended to minimize risk for kernicterus.⁹ Dapsone can be found in high concentrations in breast milk at 14.3% of the maternal dose. It is still safe to use during breastfeeding, but there is a risk of the infant developing hyperbilirubinemia/G6PD deficiency.^1,8 Thus, physicians may consider performing a G6PD screen on infants to determine if breastfeeding is safe.¹²

Fluoroquinolones—Quinolones are not contraindicated during pregnancy, but they can damage fetal cartilage and thus should be reserved for use in complicated infections when the benefits outweigh the risks.¹² Quinolones are believed to increase risk for arthropathy but are safe for use in lactation. When quinolones are digested with milk, exposure decreases below pediatric doses because of the ionized property of calcium in milk.⁸

Tumor Necrosis Factor α Inhibitors—The safety of anti–tumor necrosis factor (TNF) α biologics in pregnancy is less certain when compared with antibiotics.¹ Anti–TNF-α inhibitors such as etanercept, adalimumab, and infliximab are all labeled as FDA category B, meaning there are no well-controlled human studies of the drugs.⁹ There are limited data that support safe use of TNF-α inhibitors prior to the third trimester before maternal IgG antibodies are transferred to the fetus via the placenta.^1,13 Anti–TNF-α inhibitors may be safe when breastfeeding because the drugs have large molecular weights that prevent them from entering breast milk in large amounts. Absorption also is limited due to the infant’s digestive acids and enzymes breaking down the protein structure of the medication.⁸ Overall, TNF-α inhibitor use is still controversial and only used if the benefits outweigh the risks during pregnancy or if there is no alternative treatment.^1,3,9

Ustekinumab and Anakinra—Ustekinumab (an IL-12/IL-23 inhibitor) and anakinra (an IL-1α and IL-1β inhibitor) also are FDA category B drugs and have limited data supporting their use as HS treatment in pregnancy. Anakinra may have evidence of compatibility with breastfeeding, as endogenous IL-1α inhibitor is found in colostrum and mature breast milk.¹

Immunosuppressants

Immunosuppressants that are used to treat HS include corticosteroids and cyclosporine.

Corticosteroids—Topical corticosteroids can be used safely in lactation if they are not applied directly to the nipple or any area that makes direct contact with the infant’s mouth. Intralesional corticosteroid injections are safe for use during both pregnancy and breastfeeding to decrease inflammation of acutely flaring lesions and can be considered first-line treatment.¹ Oral glucocorticoids also can be safely used for acute flares during pregnancy; however, prolonged use is associated with pregnancy complications such as preeclampsia, eclampsia, premature delivery, and gestational diabetes.¹² There also is a small risk of oral cleft deformity in the infant; thus, potent corticosteroids are recommended in short durations during pregnancy, and there are no adverse effects if the maternal dose is less than 10 mg daily.^8,12 Systemic steroids are safe to use with breastfeeding, but patients should be advised to wait 4 hours after ingesting medication before breastfeeding.^1,8

Cyclosporine—Topical and oral calcineurin inhibitors such as cyclosporine have low risk for transmission into breast milk; however, potential effects of exposure through breast milk are unknown. For that reason, manufacturers state that cyclosporine use is contraindicated during lactation.⁸ If cyclosporine is to be used by a breastfeeding woman, monitoring cyclosporine concentrations in the infant is suggested to ensure that the exposure is less than 5% to 10% of the therapeutic dose.¹³ The use of cyclosporine has been extensively studied in pregnant transplant patients and is considered relatively safe for use in pregnancy.¹⁴ Cyclosporine is lipid soluble and thus is quickly metabolized and spread throughout the body; it can easily cross the placenta.^9,13 Blood concentration in the fetus is 30% to 64% that of the maternal circulation. However, cyclosporine is only toxic to the fetus at maternally toxic doses, which can result in low birth weight and increased prenatal and postnatal mortality.¹³

Isotretinoin, Oral Contraceptive Pills, and Spironolactone

Isotretinoin and hormonal treatments such as oral contraceptive pills and spironolactone (an androgen receptor blocker) commonly are used to treat HS, but all are contraindicated in pregnancy and lactation. Isotretinoin is a well-established teratogen, but adverse effects on nursing babies have not been described. However, the manufacturer of isotretinoin advises against its use in lactation. Oral contraceptive pill use in early pregnancy is associated with increased risk for Down syndrome. Oral contraceptive pill use also is contraindicated in lactation for 2 reasons: decreased milk production and risk for fetal feminization. Antiandrogenic agents such as spironolactone have been shown to be associated with hypospadias and feminization of the male fetus.⁷

COMMENT

Women with HS usually require ongoing medical treatment during pregnancy and immediately postpartum; thus, it is important that treatments are proven to be safe for use in this specific population. Current management guidelines are not entirely suitable for pregnant and breastfeeding women given that many HS drugs have teratogenic effects and/or can be excreted into breast milk.¹ Several treatments have uncertain safety profiles in pregnancy and breastfeeding, which calls for dermatologists to change or create new regimens for their patients. Close management also is necessary to prevent excess inflammation of breast tissue and milk fistula formation, which would hinder normal breastfeeding.

The eTable lists medications used to treat HS. The FDA category is listed next to each drug. However, it should be noted that these FDA letter categories were replaced with the Pregnancy and Lactation Labeling Rule in 2015. The letter ratings were deemed overly simplistic and replaced with narrative-based labeling that provides more detailed adverse effects and clinical considerations.⁹

Risk Factors of HS—Predisposing risk factors for HS flares that are controllable include obesity and smoking.² Pregnancy weight gain may cause increased skin maceration at intertriginous sites, which can contribute to worsening HS symptoms.^1,5 Adipocytes play a role in HS exacerbation by promoting secretion of TNF-α, leading to increased inflammation.⁵ Dermatologists can help prevent postpartum HS flares by monitoring weight gain during pregnancy, encouraging smoking cessation, and promoting weight and nutrition goals as set by an obstetrician.¹ In addition to medications, management of HS should include emotional support and education on wearing loose-fitting clothing to avoid irritation of the affected areas.³ An emphasis on dermatologist counseling for all patients with HS, even for those with milder disease, can reduce exacerbations during pregnancy.⁵

CONCLUSION

The selection of dermatologic drugs for the treatment of HS in the setting of pregnancy involves complex decision-making. Dermatologists need more guidelines and proven safety data in human trials, especially regarding use of biologics and immunosuppressants to better treat HS in pregnancy. With more data, they can create more evidence-based treatment regimens to help prevent postpartum exacerbations of HS. Thus, patients can breastfeed their infants comfortably and without any risks of impaired child development. In the meantime, dermatologists can continue to work together with obstetricians and psychiatrists to decrease disease flares through counseling patients on nutrition and weight gain and providing emotional support.

The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.¹

Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.¹ We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.

Case Report

A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.

Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).

The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.

Comment

The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.^2,3

There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.⁴ Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.^5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.

BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.²

Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.⁷ There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.^2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.

Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.¹⁰ A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.¹¹

Conclusion

We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.

The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.¹

Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.¹ We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.

Case Report

A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.

Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).

The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.

Comment

The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.^2,3

There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.⁴ Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.^5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.

BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.²

Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.⁷ There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.^2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.

Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.¹⁰ A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.¹¹

Conclusion

We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.

The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.¹

Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.¹ We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.

Case Report

A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.

Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).

The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.

Comment

The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.^2,3

There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.⁴ Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.^5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.

BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.²

Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.⁷ There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.^2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.

Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.¹⁰ A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.¹¹

Conclusion

We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

“Adipose tissue is an underappreciated and misunderstood organ.” It’s with these words that Aaron M. Cypess, MD, PhD, begins his recent review published in the New England Journal of Medicine.

As obesity rates steadily rise, “the riskiest approach to human adipose tissue is to dismiss its importance,” he adds, especially because there has been “an explosive growth” in our understanding of white and brown adipose tissue over the past 5 to 10 years.

This news organization asked Dr. Cypess, a National Institutes of Health (NIH) scientist whose research focuses on brown fat, to discuss some of the main points in his review, titled, “Reassessing Human Adipose Tissue,” and clear up some misconceptions about fat.

You write that, for people who struggle to lose weight, “fat is often a source of misery, not marvel.” Why is fat a marvel?

When I started medical school in 1992, fat was just a thing that stored calories. You had to get it out of the way when you operated on the stomach or intestines. Now we know it’s not just one cell, it’s multiple types of cells, including immune cells and some blood cells. There’s cell turnover, and cells can get bigger or smaller, so it’s a dynamic tissue. It impacts the immune system and affects insulin sensitivity.

Why use the term “adipose tissue” and not just “fat”?

People think of fat cells and that’s it. However, adipose tissue (fat) has multiple cell types, and they each matter. There are adipocytes (fat cells) – which can be white, brown, beige, or pink – as well as immune cells, fibroblasts, blood vessels, and parts of nerve cells.

The main function of white adipose tissue is to store energy in the form of triglycerides. Brown adipose tissue consumes glucose and triglycerides, generating heat. Brown fat cells within depots of white fat are termed brite cells (a portmanteau of brown and white) or beige cells. Pink fat cells have been found in breast tissue in mice.

What do we now know about white fat and brown fat? Can brown fat change to white fat or vice versa?

White adipose tissue is commonly separated into visceral fat and subcutaneous fat, which have negative and neutral or positive metabolic effects, respectively. It is capable of more than doubling in mass and then returning to baseline.

White adipocyte-derived hormones include leptin, which is low in starvation, and adiponectin, which regulates glucose and lipid metabolism. White adipose tissue is essential for the proper function of the reproductive system, including secretion of hormones and lactation.

Brown adipose tissue protects newborns from cold as they develop the ability to shiver, and in adults it is found in depots in the neck, shoulders, posterior thorax, and abdomen. The amount of brown adipose tissue varies according to sex and lowers with increasing age and increasing body mass index.

There is much more white fat in the body than brown fat. It appears that activating brown fat leads to beneficial effects on metabolism, though we don’t know yet all the steps for how that happens.

In mice, you’ve got white fat depots and brown fat depots, and some brown fat can be found in the white fat.

With humans it’s much more complicated, and I’ve seen this in the operating room myself, and on slides. Where you find brown fat cells you also find a certain proportion of white fat cells, not an exclusive brown fat depot like you see in a mouse.

It is hotly debated right now whether brown fat can change to white fat and vice versa (transdifferentiation). The beige fat cells are supposed to be the kind that can shuttle between more white-like or brown-like. They can sometimes be white or sometimes brown. It can be very contentious in [scientific] papers and meetings.

Are humans born with all the fat cells they will ever have?

No. New fat cells are made throughout our lives. When the white adipocytes store too much triglyceride, they get really big and they get “sick” and die faster. It’s the rate at which the white cells take up the fat to store it and then get rid of it that can impact whether someone gains a lot of weight and whether they can successfully lose it after reasonable effort.

The average lifespan of a white fat cell is 15 years. We have no idea yet of the lifespan of a brown fat cell.

Is there a single “fat gene”? What role do fat genes play in the likelihood of developing metabolic diseases and type 2 diabetes?

Genes are very important for influencing the development of obesity and probably influence 50%-70% of obesity, based on studies in populations of predominantly European origin. But that high percentage reflects the impact of hundreds of genes. For most people, there is no one gene that exerts all of the effects. There are extremely rare diseases where one gene is responsible. Currently, only 20% of the entire phenotypic variation in obesity can be explained by the thousands of loci identified so far.

Why is it “correct but too simplistic” to attribute the increasing rates of obesity to excessive triglyceride storage in white adipose tissue?

Saying obesity is caused by too much triglyceride storage ignores the reasons how and why the triglycerides got there. There are likely to be multiple contributing factors to drive obesity, and those have billions of dollars of policy implications. Is obesity resulting from portion sizes? Then we should work on educating the public on how to estimate their caloric intake. Is it the types of foods, such as ultra-processed foods? Then we can discourage eating certain food groups while promoting others. Is it about physical activity? Then we should prioritize exercise programs.

Why is obesity “not simply a failure of will power”?

Genetic factors in adipose tissue impact how easy it is to store triglycerides, how easy it is to get fat out of the tissue and burn it up, and what kinds of hormones are released by the tissue to regulate appetite, insulin resistance, and inflammation. Ten different people can all overeat the same amount of the same foods, yet there will be differences in the amount of weight gain and metabolic complications experienced. And at the brain level, some people will feel “full” sooner than others.

How can excess adipose tissue lead to disease? Do some people have “metabolically healthy obesity”?

Excess adipose tissue leads to chronic inflammation that can then cause insulin resistance, hypertension, fatty liver disease, and other complications. It appears that there are metabolically healthy obese people, but it is not clear if that is only a temporary state.

Could long-term brown adipose tissue activation help treat obesity or related metabolic disease?

Our research group at the NIH and others have shown that long-term brown adipose tissue activation produces metabolic benefit such as improved insulin resistance, lower plasma glucose, and higher HDL [good] cholesterol. However, there is no evidence yet that it will lead to actual weight loss.

We are trying to use brown adipose tissue activation to treat obesity-related metabolic disease to see if it could lead to reduction in inflammation, improvement in the cholesterol profile, and decrease in blood pressure.

A large observational study published Jan. 4, 2021, in Nature Medicine by Paul Cohen’s group at Rockefeller University, in tens of thousands of people at Memorial Sloan Kettering Cancer Center, showed that people who had brown fat were generally healthier and had less high blood pressure and less cardiovascular disease. This study could not show causation, but at every BMI, people were healthier if they had more brown fat than if they had less. So, there’s something going on. We’re still trying to figure that out.

Dr. Cypess has no reported no relevant financial relationships.

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

“Adipose tissue is an underappreciated and misunderstood organ.” It’s with these words that Aaron M. Cypess, MD, PhD, begins his recent review published in the New England Journal of Medicine.

As obesity rates steadily rise, “the riskiest approach to human adipose tissue is to dismiss its importance,” he adds, especially because there has been “an explosive growth” in our understanding of white and brown adipose tissue over the past 5 to 10 years.

This news organization asked Dr. Cypess, a National Institutes of Health (NIH) scientist whose research focuses on brown fat, to discuss some of the main points in his review, titled, “Reassessing Human Adipose Tissue,” and clear up some misconceptions about fat.

You write that, for people who struggle to lose weight, “fat is often a source of misery, not marvel.” Why is fat a marvel?

When I started medical school in 1992, fat was just a thing that stored calories. You had to get it out of the way when you operated on the stomach or intestines. Now we know it’s not just one cell, it’s multiple types of cells, including immune cells and some blood cells. There’s cell turnover, and cells can get bigger or smaller, so it’s a dynamic tissue. It impacts the immune system and affects insulin sensitivity.

Why use the term “adipose tissue” and not just “fat”?

People think of fat cells and that’s it. However, adipose tissue (fat) has multiple cell types, and they each matter. There are adipocytes (fat cells) – which can be white, brown, beige, or pink – as well as immune cells, fibroblasts, blood vessels, and parts of nerve cells.

The main function of white adipose tissue is to store energy in the form of triglycerides. Brown adipose tissue consumes glucose and triglycerides, generating heat. Brown fat cells within depots of white fat are termed brite cells (a portmanteau of brown and white) or beige cells. Pink fat cells have been found in breast tissue in mice.

What do we now know about white fat and brown fat? Can brown fat change to white fat or vice versa?

White adipose tissue is commonly separated into visceral fat and subcutaneous fat, which have negative and neutral or positive metabolic effects, respectively. It is capable of more than doubling in mass and then returning to baseline.

White adipocyte-derived hormones include leptin, which is low in starvation, and adiponectin, which regulates glucose and lipid metabolism. White adipose tissue is essential for the proper function of the reproductive system, including secretion of hormones and lactation.

Brown adipose tissue protects newborns from cold as they develop the ability to shiver, and in adults it is found in depots in the neck, shoulders, posterior thorax, and abdomen. The amount of brown adipose tissue varies according to sex and lowers with increasing age and increasing body mass index.

There is much more white fat in the body than brown fat. It appears that activating brown fat leads to beneficial effects on metabolism, though we don’t know yet all the steps for how that happens.

In mice, you’ve got white fat depots and brown fat depots, and some brown fat can be found in the white fat.

With humans it’s much more complicated, and I’ve seen this in the operating room myself, and on slides. Where you find brown fat cells you also find a certain proportion of white fat cells, not an exclusive brown fat depot like you see in a mouse.

It is hotly debated right now whether brown fat can change to white fat and vice versa (transdifferentiation). The beige fat cells are supposed to be the kind that can shuttle between more white-like or brown-like. They can sometimes be white or sometimes brown. It can be very contentious in [scientific] papers and meetings.

Are humans born with all the fat cells they will ever have?

No. New fat cells are made throughout our lives. When the white adipocytes store too much triglyceride, they get really big and they get “sick” and die faster. It’s the rate at which the white cells take up the fat to store it and then get rid of it that can impact whether someone gains a lot of weight and whether they can successfully lose it after reasonable effort.

The average lifespan of a white fat cell is 15 years. We have no idea yet of the lifespan of a brown fat cell.

Is there a single “fat gene”? What role do fat genes play in the likelihood of developing metabolic diseases and type 2 diabetes?

Genes are very important for influencing the development of obesity and probably influence 50%-70% of obesity, based on studies in populations of predominantly European origin. But that high percentage reflects the impact of hundreds of genes. For most people, there is no one gene that exerts all of the effects. There are extremely rare diseases where one gene is responsible. Currently, only 20% of the entire phenotypic variation in obesity can be explained by the thousands of loci identified so far.

Why is it “correct but too simplistic” to attribute the increasing rates of obesity to excessive triglyceride storage in white adipose tissue?

Saying obesity is caused by too much triglyceride storage ignores the reasons how and why the triglycerides got there. There are likely to be multiple contributing factors to drive obesity, and those have billions of dollars of policy implications. Is obesity resulting from portion sizes? Then we should work on educating the public on how to estimate their caloric intake. Is it the types of foods, such as ultra-processed foods? Then we can discourage eating certain food groups while promoting others. Is it about physical activity? Then we should prioritize exercise programs.

Why is obesity “not simply a failure of will power”?

Genetic factors in adipose tissue impact how easy it is to store triglycerides, how easy it is to get fat out of the tissue and burn it up, and what kinds of hormones are released by the tissue to regulate appetite, insulin resistance, and inflammation. Ten different people can all overeat the same amount of the same foods, yet there will be differences in the amount of weight gain and metabolic complications experienced. And at the brain level, some people will feel “full” sooner than others.

How can excess adipose tissue lead to disease? Do some people have “metabolically healthy obesity”?

Excess adipose tissue leads to chronic inflammation that can then cause insulin resistance, hypertension, fatty liver disease, and other complications. It appears that there are metabolically healthy obese people, but it is not clear if that is only a temporary state.

Could long-term brown adipose tissue activation help treat obesity or related metabolic disease?

Our research group at the NIH and others have shown that long-term brown adipose tissue activation produces metabolic benefit such as improved insulin resistance, lower plasma glucose, and higher HDL [good] cholesterol. However, there is no evidence yet that it will lead to actual weight loss.

We are trying to use brown adipose tissue activation to treat obesity-related metabolic disease to see if it could lead to reduction in inflammation, improvement in the cholesterol profile, and decrease in blood pressure.

A large observational study published Jan. 4, 2021, in Nature Medicine by Paul Cohen’s group at Rockefeller University, in tens of thousands of people at Memorial Sloan Kettering Cancer Center, showed that people who had brown fat were generally healthier and had less high blood pressure and less cardiovascular disease. This study could not show causation, but at every BMI, people were healthier if they had more brown fat than if they had less. So, there’s something going on. We’re still trying to figure that out.

Dr. Cypess has no reported no relevant financial relationships.

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

“Adipose tissue is an underappreciated and misunderstood organ.” It’s with these words that Aaron M. Cypess, MD, PhD, begins his recent review published in the New England Journal of Medicine.

As obesity rates steadily rise, “the riskiest approach to human adipose tissue is to dismiss its importance,” he adds, especially because there has been “an explosive growth” in our understanding of white and brown adipose tissue over the past 5 to 10 years.

This news organization asked Dr. Cypess, a National Institutes of Health (NIH) scientist whose research focuses on brown fat, to discuss some of the main points in his review, titled, “Reassessing Human Adipose Tissue,” and clear up some misconceptions about fat.

You write that, for people who struggle to lose weight, “fat is often a source of misery, not marvel.” Why is fat a marvel?

When I started medical school in 1992, fat was just a thing that stored calories. You had to get it out of the way when you operated on the stomach or intestines. Now we know it’s not just one cell, it’s multiple types of cells, including immune cells and some blood cells. There’s cell turnover, and cells can get bigger or smaller, so it’s a dynamic tissue. It impacts the immune system and affects insulin sensitivity.

Why use the term “adipose tissue” and not just “fat”?

People think of fat cells and that’s it. However, adipose tissue (fat) has multiple cell types, and they each matter. There are adipocytes (fat cells) – which can be white, brown, beige, or pink – as well as immune cells, fibroblasts, blood vessels, and parts of nerve cells.

The main function of white adipose tissue is to store energy in the form of triglycerides. Brown adipose tissue consumes glucose and triglycerides, generating heat. Brown fat cells within depots of white fat are termed brite cells (a portmanteau of brown and white) or beige cells. Pink fat cells have been found in breast tissue in mice.

What do we now know about white fat and brown fat? Can brown fat change to white fat or vice versa?

White adipose tissue is commonly separated into visceral fat and subcutaneous fat, which have negative and neutral or positive metabolic effects, respectively. It is capable of more than doubling in mass and then returning to baseline.

White adipocyte-derived hormones include leptin, which is low in starvation, and adiponectin, which regulates glucose and lipid metabolism. White adipose tissue is essential for the proper function of the reproductive system, including secretion of hormones and lactation.

Brown adipose tissue protects newborns from cold as they develop the ability to shiver, and in adults it is found in depots in the neck, shoulders, posterior thorax, and abdomen. The amount of brown adipose tissue varies according to sex and lowers with increasing age and increasing body mass index.

There is much more white fat in the body than brown fat. It appears that activating brown fat leads to beneficial effects on metabolism, though we don’t know yet all the steps for how that happens.

In mice, you’ve got white fat depots and brown fat depots, and some brown fat can be found in the white fat.

With humans it’s much more complicated, and I’ve seen this in the operating room myself, and on slides. Where you find brown fat cells you also find a certain proportion of white fat cells, not an exclusive brown fat depot like you see in a mouse.

It is hotly debated right now whether brown fat can change to white fat and vice versa (transdifferentiation). The beige fat cells are supposed to be the kind that can shuttle between more white-like or brown-like. They can sometimes be white or sometimes brown. It can be very contentious in [scientific] papers and meetings.

Are humans born with all the fat cells they will ever have?

No. New fat cells are made throughout our lives. When the white adipocytes store too much triglyceride, they get really big and they get “sick” and die faster. It’s the rate at which the white cells take up the fat to store it and then get rid of it that can impact whether someone gains a lot of weight and whether they can successfully lose it after reasonable effort.

The average lifespan of a white fat cell is 15 years. We have no idea yet of the lifespan of a brown fat cell.

Is there a single “fat gene”? What role do fat genes play in the likelihood of developing metabolic diseases and type 2 diabetes?

Genes are very important for influencing the development of obesity and probably influence 50%-70% of obesity, based on studies in populations of predominantly European origin. But that high percentage reflects the impact of hundreds of genes. For most people, there is no one gene that exerts all of the effects. There are extremely rare diseases where one gene is responsible. Currently, only 20% of the entire phenotypic variation in obesity can be explained by the thousands of loci identified so far.

Why is it “correct but too simplistic” to attribute the increasing rates of obesity to excessive triglyceride storage in white adipose tissue?

Saying obesity is caused by too much triglyceride storage ignores the reasons how and why the triglycerides got there. There are likely to be multiple contributing factors to drive obesity, and those have billions of dollars of policy implications. Is obesity resulting from portion sizes? Then we should work on educating the public on how to estimate their caloric intake. Is it the types of foods, such as ultra-processed foods? Then we can discourage eating certain food groups while promoting others. Is it about physical activity? Then we should prioritize exercise programs.

Why is obesity “not simply a failure of will power”?

Genetic factors in adipose tissue impact how easy it is to store triglycerides, how easy it is to get fat out of the tissue and burn it up, and what kinds of hormones are released by the tissue to regulate appetite, insulin resistance, and inflammation. Ten different people can all overeat the same amount of the same foods, yet there will be differences in the amount of weight gain and metabolic complications experienced. And at the brain level, some people will feel “full” sooner than others.

How can excess adipose tissue lead to disease? Do some people have “metabolically healthy obesity”?

Excess adipose tissue leads to chronic inflammation that can then cause insulin resistance, hypertension, fatty liver disease, and other complications. It appears that there are metabolically healthy obese people, but it is not clear if that is only a temporary state.

Could long-term brown adipose tissue activation help treat obesity or related metabolic disease?

Our research group at the NIH and others have shown that long-term brown adipose tissue activation produces metabolic benefit such as improved insulin resistance, lower plasma glucose, and higher HDL [good] cholesterol. However, there is no evidence yet that it will lead to actual weight loss.

We are trying to use brown adipose tissue activation to treat obesity-related metabolic disease to see if it could lead to reduction in inflammation, improvement in the cholesterol profile, and decrease in blood pressure.

A large observational study published Jan. 4, 2021, in Nature Medicine by Paul Cohen’s group at Rockefeller University, in tens of thousands of people at Memorial Sloan Kettering Cancer Center, showed that people who had brown fat were generally healthier and had less high blood pressure and less cardiovascular disease. This study could not show causation, but at every BMI, people were healthier if they had more brown fat than if they had less. So, there’s something going on. We’re still trying to figure that out.

Dr. Cypess has no reported no relevant financial relationships.

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

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

Although the Sentinel cerebral embolism protection (CEP) device may not significantly reduce the overall stroke rate in patients after they’ve had transcatheter aortic valve replacement (TAVR), the device may improve survival and reduce the severity of procedure-related stroke, a retrospective database study reported.

Investigators led by Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic, analyzed outcomes of 136,382 patients in the Nationwide Readmissions Database who had TAVR in 2018-2019. The dataset included 10,201 people who received the Sentinel CEP device during TAVR.

The proportion of patients who had a stroke after TAVR was similar in both groups – 1.85% (189) in the CEP group and 1.94% (1,447) in the CEP nonusers – but, as Dr. Kapadia pointed out, the stroke outcomes between the two groups were noticeably different.

“Interestingly enough, what we found was that the people with the CEPs who had a stroke had half the mortality, and they were going home at a significantly higher rate, than the people who had a stroke and didn’t have CEPs,” Dr. Kapadia said in an interview. A previous registry study of 276,316 TAVR patients reported the overall rate of post-TAVR stroke declined from 2.75% to 2.3% over an 8-year period. The CEP device, approved in December 2017, had been available in the last 2 years of that study.

In the current retrospective database study, CEP patients went home after their post-TAVR strokes at a rate of 28.2%, compared with 19.9% for those who didn’t have CEP (P = .011). The in-hospital death rates were 6.3% and 11.8% for the respective groups (P = .023), and the 30-day readmission rates were 15.9% and 16.8% (P = .91). “The readmission rate is similar, but if you survive you get admitted,” Dr. Kapadia reported in a research letter published in JACC: Cardiovascular Interventions.

CEP involves inserting a catheter in the right wrist during TAVR. The catheter deploys two filters, one in the left carotid artery, the other on the right carotid and radial arteries, to capture embolic debris. After the aortic valve is seated and the TAVR completed, the CEP filters are removed.

Potential effectiveness of filters

The study builds on work by Dr. Kapadia and colleagues reported in the PARTNER trial, which showed that CEP filters consistently captured embolized debris resulting in smaller brain lesions after TAVR than no filters. The hypothesis for the latest study, Dr. Kapadia said, “was that, even though the stroke rates may be very similar between the TAVR patients who had CEP and those who did not, the filter removed the large embolic particles, although there were small particles. In those cases, the consequence of stroke would be much less in the sense that you would have minor strokes, and you would either not die from the stroke or you would be able to walk home safely if you did have a stroke.”

In Dr. Kapadia’s experience, the filters capture up to 80% of embolic debris. The Cleveland Clinic used CEP in 96.5% of its TAVR cases in 2021, he said, adding that national rates are considerably lower because Medicare doesn’t reimburse for the procedure. An observational registry study reported that 13% of TAVR procedures used CEP by December 2019.

Dr. Kapadia said that the PROTECTED TAVR trial of the CEP device has completed data gathering and should report results later in 2022. The study randomized 3,000 patients to TAVR with or without CEP.

Dr. Kapadia noted that the findings require further study to validate them. “If it is all true, it will change the practice; it will make TAVR safer.”

David J. Cohen, MD, MSc, director of clinical and outcome research at the Cardiovascular Research Foundation in New York, called the study findings “provocative,” adding: “It makes points that we’ve seen in previous studies and certainly suggests there may be an important benefit of cerebral embolism protection that has not been well established to date.” Dr. Cohen is also director of academic affairs at St. Francis Hospital in Roslyn, N.Y.

The primary two findings of the study – lower risk of death and greater likelihood of discharge to home in CEP patients who had strokes after TAVR – “suggest that, while data on whether embolic protection actually prevents strokes is controversial and not at all definitive, these data suggest that perhaps one additional mechanism of benefit is that it’s making it much less severe when stroke occurs. That would obviously be of tremendous value.”

The findings are in line with other “suggestions that have not yet been explained,” Dr. Cohen said. “They may provide sort of a unifying explanation of why embolic protection may not prevent as many strokes as we thought but they may still be a very valuable adjunct.”

Boston Scientific distributes the Sentinel CEP device used in the study. Dr. Kapadia is the principal investigator of the PROTECTED TAVR trial, sponsored by Boston Scientific. Dr. Kapadia and study coauthors reported no other disclosures. Dr. Cohen is a consultant to Boston Scientific.

Although the Sentinel cerebral embolism protection (CEP) device may not significantly reduce the overall stroke rate in patients after they’ve had transcatheter aortic valve replacement (TAVR), the device may improve survival and reduce the severity of procedure-related stroke, a retrospective database study reported.

Investigators led by Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic, analyzed outcomes of 136,382 patients in the Nationwide Readmissions Database who had TAVR in 2018-2019. The dataset included 10,201 people who received the Sentinel CEP device during TAVR.

The proportion of patients who had a stroke after TAVR was similar in both groups – 1.85% (189) in the CEP group and 1.94% (1,447) in the CEP nonusers – but, as Dr. Kapadia pointed out, the stroke outcomes between the two groups were noticeably different.

“Interestingly enough, what we found was that the people with the CEPs who had a stroke had half the mortality, and they were going home at a significantly higher rate, than the people who had a stroke and didn’t have CEPs,” Dr. Kapadia said in an interview. A previous registry study of 276,316 TAVR patients reported the overall rate of post-TAVR stroke declined from 2.75% to 2.3% over an 8-year period. The CEP device, approved in December 2017, had been available in the last 2 years of that study.

In the current retrospective database study, CEP patients went home after their post-TAVR strokes at a rate of 28.2%, compared with 19.9% for those who didn’t have CEP (P = .011). The in-hospital death rates were 6.3% and 11.8% for the respective groups (P = .023), and the 30-day readmission rates were 15.9% and 16.8% (P = .91). “The readmission rate is similar, but if you survive you get admitted,” Dr. Kapadia reported in a research letter published in JACC: Cardiovascular Interventions.

CEP involves inserting a catheter in the right wrist during TAVR. The catheter deploys two filters, one in the left carotid artery, the other on the right carotid and radial arteries, to capture embolic debris. After the aortic valve is seated and the TAVR completed, the CEP filters are removed.

Potential effectiveness of filters

The study builds on work by Dr. Kapadia and colleagues reported in the PARTNER trial, which showed that CEP filters consistently captured embolized debris resulting in smaller brain lesions after TAVR than no filters. The hypothesis for the latest study, Dr. Kapadia said, “was that, even though the stroke rates may be very similar between the TAVR patients who had CEP and those who did not, the filter removed the large embolic particles, although there were small particles. In those cases, the consequence of stroke would be much less in the sense that you would have minor strokes, and you would either not die from the stroke or you would be able to walk home safely if you did have a stroke.”

In Dr. Kapadia’s experience, the filters capture up to 80% of embolic debris. The Cleveland Clinic used CEP in 96.5% of its TAVR cases in 2021, he said, adding that national rates are considerably lower because Medicare doesn’t reimburse for the procedure. An observational registry study reported that 13% of TAVR procedures used CEP by December 2019.

Dr. Kapadia said that the PROTECTED TAVR trial of the CEP device has completed data gathering and should report results later in 2022. The study randomized 3,000 patients to TAVR with or without CEP.

Dr. Kapadia noted that the findings require further study to validate them. “If it is all true, it will change the practice; it will make TAVR safer.”

David J. Cohen, MD, MSc, director of clinical and outcome research at the Cardiovascular Research Foundation in New York, called the study findings “provocative,” adding: “It makes points that we’ve seen in previous studies and certainly suggests there may be an important benefit of cerebral embolism protection that has not been well established to date.” Dr. Cohen is also director of academic affairs at St. Francis Hospital in Roslyn, N.Y.

The primary two findings of the study – lower risk of death and greater likelihood of discharge to home in CEP patients who had strokes after TAVR – “suggest that, while data on whether embolic protection actually prevents strokes is controversial and not at all definitive, these data suggest that perhaps one additional mechanism of benefit is that it’s making it much less severe when stroke occurs. That would obviously be of tremendous value.”

The findings are in line with other “suggestions that have not yet been explained,” Dr. Cohen said. “They may provide sort of a unifying explanation of why embolic protection may not prevent as many strokes as we thought but they may still be a very valuable adjunct.”

Boston Scientific distributes the Sentinel CEP device used in the study. Dr. Kapadia is the principal investigator of the PROTECTED TAVR trial, sponsored by Boston Scientific. Dr. Kapadia and study coauthors reported no other disclosures. Dr. Cohen is a consultant to Boston Scientific.

Although the Sentinel cerebral embolism protection (CEP) device may not significantly reduce the overall stroke rate in patients after they’ve had transcatheter aortic valve replacement (TAVR), the device may improve survival and reduce the severity of procedure-related stroke, a retrospective database study reported.

Investigators led by Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic, analyzed outcomes of 136,382 patients in the Nationwide Readmissions Database who had TAVR in 2018-2019. The dataset included 10,201 people who received the Sentinel CEP device during TAVR.

The proportion of patients who had a stroke after TAVR was similar in both groups – 1.85% (189) in the CEP group and 1.94% (1,447) in the CEP nonusers – but, as Dr. Kapadia pointed out, the stroke outcomes between the two groups were noticeably different.

“Interestingly enough, what we found was that the people with the CEPs who had a stroke had half the mortality, and they were going home at a significantly higher rate, than the people who had a stroke and didn’t have CEPs,” Dr. Kapadia said in an interview. A previous registry study of 276,316 TAVR patients reported the overall rate of post-TAVR stroke declined from 2.75% to 2.3% over an 8-year period. The CEP device, approved in December 2017, had been available in the last 2 years of that study.

In the current retrospective database study, CEP patients went home after their post-TAVR strokes at a rate of 28.2%, compared with 19.9% for those who didn’t have CEP (P = .011). The in-hospital death rates were 6.3% and 11.8% for the respective groups (P = .023), and the 30-day readmission rates were 15.9% and 16.8% (P = .91). “The readmission rate is similar, but if you survive you get admitted,” Dr. Kapadia reported in a research letter published in JACC: Cardiovascular Interventions.

CEP involves inserting a catheter in the right wrist during TAVR. The catheter deploys two filters, one in the left carotid artery, the other on the right carotid and radial arteries, to capture embolic debris. After the aortic valve is seated and the TAVR completed, the CEP filters are removed.

Potential effectiveness of filters

The study builds on work by Dr. Kapadia and colleagues reported in the PARTNER trial, which showed that CEP filters consistently captured embolized debris resulting in smaller brain lesions after TAVR than no filters. The hypothesis for the latest study, Dr. Kapadia said, “was that, even though the stroke rates may be very similar between the TAVR patients who had CEP and those who did not, the filter removed the large embolic particles, although there were small particles. In those cases, the consequence of stroke would be much less in the sense that you would have minor strokes, and you would either not die from the stroke or you would be able to walk home safely if you did have a stroke.”

In Dr. Kapadia’s experience, the filters capture up to 80% of embolic debris. The Cleveland Clinic used CEP in 96.5% of its TAVR cases in 2021, he said, adding that national rates are considerably lower because Medicare doesn’t reimburse for the procedure. An observational registry study reported that 13% of TAVR procedures used CEP by December 2019.

Dr. Kapadia said that the PROTECTED TAVR trial of the CEP device has completed data gathering and should report results later in 2022. The study randomized 3,000 patients to TAVR with or without CEP.

Dr. Kapadia noted that the findings require further study to validate them. “If it is all true, it will change the practice; it will make TAVR safer.”

David J. Cohen, MD, MSc, director of clinical and outcome research at the Cardiovascular Research Foundation in New York, called the study findings “provocative,” adding: “It makes points that we’ve seen in previous studies and certainly suggests there may be an important benefit of cerebral embolism protection that has not been well established to date.” Dr. Cohen is also director of academic affairs at St. Francis Hospital in Roslyn, N.Y.

The primary two findings of the study – lower risk of death and greater likelihood of discharge to home in CEP patients who had strokes after TAVR – “suggest that, while data on whether embolic protection actually prevents strokes is controversial and not at all definitive, these data suggest that perhaps one additional mechanism of benefit is that it’s making it much less severe when stroke occurs. That would obviously be of tremendous value.”

The findings are in line with other “suggestions that have not yet been explained,” Dr. Cohen said. “They may provide sort of a unifying explanation of why embolic protection may not prevent as many strokes as we thought but they may still be a very valuable adjunct.”

Boston Scientific distributes the Sentinel CEP device used in the study. Dr. Kapadia is the principal investigator of the PROTECTED TAVR trial, sponsored by Boston Scientific. Dr. Kapadia and study coauthors reported no other disclosures. Dr. Cohen is a consultant to Boston Scientific.

Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.

On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.

Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.

Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.

Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.

They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.

Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.

“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”

Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren

Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States.  Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604

Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.

On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.

Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.

Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.

Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.

They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.

Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.

“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”

Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren

Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States.  Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604

Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.

On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.

Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.

Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.

Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.

They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.

Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.

“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”

Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren

Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States.  Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.