Opinion

 

Novel drugs are innovative new products that have never before been used in clinical practice. Among the 46 that the Food and Drug Administration approved in 2017, 45 could be used in pregnancy. One, cerliponase alfa (Brineura), is indicated for pediatric patients 3 years of age or older, for treatment of late infantile neuronal ceroid lipofuscinosis type 2. It is doubtful that this drug would be used in pregnancy or during breastfeeding.

With the two exceptions noted below, there are no human pregnancy data for these drugs. It is important to consider that although high molecular weight (MW) drugs (for example, greater than 1,000) probably do not usually cross the placenta in the first half of pregnancy, they may do so in late pregnancy. The cited MWs are shown as the nearest whole number. Animal reproductive data are also cited because, although not definitive, they can provide some measure of the human embryo-fetal risk.
 

Anti-infectives

Benznidazole (same trade name) (MW 441), given orally, is indicated for pediatric patients aged 2-12 years for treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi. However, there are international reports describing its use in pregnancy and breastfeeding. No fetal harm from these exposures were noted. Nevertheless, because of the low MW and the reported animal risk, avoiding the drug during the first half of pregnancy appears to be the best choice. Delafloxacin (Baxdela) (MW 441), a fluoroquinolone antimicrobial given intravenously or orally, is indicated for acute bacterial skin infections. The animal data suggest low risk. However, like other fluoroquinolones, it is contraindicated in pregnancy and should be used only if there are no other alternatives.

Glecaprevir/pibrentasvir (Mavyret) (MWs 839, 1,113), a fixed oral dose combination of two antivirals, is indicated for the treatment of hepatitis C virus infection. The animal data suggest low risk. Letermovir (Prevymis) (MW 573) is available for oral and intravenous administration. It is indicated for cytomegalovirus infection. Animal reproduction studies suggest risk. Meropenem/vaborbactam (Vabomere) (MWs 438, 297), given intravenously, is indicated for the treatment of urinary tract infections including pyelonephritis. No malformations were observed in pregnant rats and monkeys exposed to meropenem during organogenesis. Vaborbactam did not cause embryo-fetal harm in rats but did cause a low incidence of malformations in rabbits. Ozenoxacin (Xepi) (MW 363), a cream, is indicated for the topical treatment of impetigo due to Staphylococcus aureus. Among 86 nonpregnant subjects, no systemic absorption was observed in 84, and negligible absorption was observed at the level of detection in 2. Animal reproduction studies were not conducted.

Sofosbuvir/velpatasvir /voxilaprevir (Vosevi) (MWs 529, 883, 869), a fixed oral dose combination of three antivirals, is indicated for the treatment of hepatitis C virus infection. The MWs suggest that all three will cross the human placenta. The animal data suggest low risk. Secnidazole (Solosec) (MW 185), given orally, is indicated for the treatment of bacterial vaginosis. It is closely related to metronidazole. No evidence of embryo-fetal toxicity was observed in rats and rabbits, suggesting that the human risk is low. In a report from Brazil, 134 pregnant women with bacterial vaginosis were treated with secnidazole, metronidazole, or tinidazole in the second and third trimesters. Treatment significantly decreased the incidence of premature rupture of membranes, preterm labor, preterm birth, and low birth weight. No fetal harm was reported.
 

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, in pregnancy and breastfeeding.]

Abemaciclib (Verzenio) (MW 507), an oral inhibitor of cyclin-dependent kinases, is indicated for the treatment of breast cancer. The drug is teratogenic in rats. Acalabrutinib (Calquence) (MW 466) is an oral kinase inhibitor indicated for mantle cell lymphoma. The drug had no effect on the rat embryo-fetus but caused decreased fetal body weights and delayed skeletal ossification in rabbits. Avelumab (Bavencio) (MW 147,000) is given intravenously for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma. Animal reproduction studies have not been conducted. However, based on its mechanism of action, fetal exposure may increase the risk of developing immune-related disorders or altering the normal immune response.

 

Brigatinib (Alunbrig) (MW 584) is given orally for the treatment of metastatic non–small-cell lung cancer. In rats, doses less than or slightly above the human exposure caused multiple anomalies in the fetuses of pregnant rats. Copanlisib (Aliqopa) (MW 553) is a kinase inhibitor that is given intravenously for relapsed follicular lymphoma. In rats during organogenesis, doses based on body surface area that were a fraction of the human dose caused embryo-fetal death and fetal defects. Durvalumab (Imfinzi) (MW 146,000), given intravenously, is indicated for the treatment of metastatic urothelial carcinoma and non–small-cell lung cancer. Monkeys given the drug from organogenesis through delivery experienced increased premature birth, fetal loss, and premature neonatal death. Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose.

Enasidenib (Idhifa) (MW 569), given orally, is indicated for the treatment of myeloid leukemia. The drug caused maternal toxicity and adverse embryo-fetal effects (postimplantation loss, resorptions, decrease viable fetuses, lower fetal birth weights, and skeletal variations) in rats and spontaneous abortions in rabbits. Inotuzumab ozogamicin (Besponsa) (MW 160,000), given intravenously, is indicated for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The drug caused fetal harm in rats but not in rabbits. Midostaurin (Rydapt) (MW 571) is an oral kinase inhibitor indicated for myeloid leukemia. In rats, a dose given during the first week of pregnancy that was a small fraction of the human exposure caused pre- and postimplantation loss. When very small doses were given during organogenesis to rats and rabbits there was significant maternal and fetal toxicity.

Neratinib (Nerlynx) (MW 673) is an oral kinase inhibitor for breast cancer. Although the drug did not cause embryo-fetal toxicity in rats, it did cause this toxicity in rabbits. Doses that resulted in exposures that were less than the human exposure caused maternal toxicity, abortions, and embryo-fetal death. Lower doses caused multiple fetal anomalies. Niraparib (Zejula) (MW 511) is indicated for treatment of epithelial ovarian, fallopian, or peritoneal cancer. Because of the potential human embryo-fetal risk based on its mechanism of action, pregnant animal studies were not conducted. Women with reproductive potential should use effective contraception during treatment and for 6 months after the last dose. Ribociclib (Kisqali) (MW 553) is an oral kinase inhibitor indicated for postmenopausal women with breast cancer. In rats, the drug cause reduced fetal weights and skeletal changes. Increased incidences of fetal abnormalities and lower fetal weights were observed in rabbits.
 

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046) is a naturally occurring peptide hormone given as an intravenous infusion. It is indicated as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. Animal reproduction studies have not been conducted. Because septic or other distributive shock is a medical emergency that can be fatal, the use of this agent in pregnancy should not be withheld.

 

Central nervous system

Deutetrabenazine (Austedo) (MW 324) is an oral drug indicated for the treatment of chorea associated with Huntington’s disease and for tardive dyskinesia. When given to rats during organogenesis there was no clear effect on embryo-fetal development.

Edaravone (Radicava) (MW 174), given as an intravenous infusion, is indicated for the treatment of amyotrophic lateral sclerosis. Doses that were not maternal toxic did not cause embryo-fetal toxicity in rats and rabbits. However, the no-effect dose for developmental toxicity was less than the recommended human dose. Naldemedine (Symproic) (MW 743) is an opioid antagonist indicated for the treatment of opioid-induced constipation. The drug crosses the human placenta and may precipitate opioid withdrawal in the fetus. The drug caused no embryo-fetal adverse effects, even at high doses, in pregnant rats and rabbits.

Ocrelizumab (Ocrevus) (MW 145,000), an intravenous agent, is used to treat patients with multiple sclerosis. The MW is high but immunoglobulins are known to cross the placenta. When given to monkeys at doses similar to or greater than the human dose, there was increased perinatal mortality, depletion of B-cell populations, and renal, bone marrow, and testicular toxicity in the offspring in the absence of maternal toxicity. Safinamide (Xadago) (MW 399) is an oral drug indicated as adjunctive treatment to levodopa/carbidopa in Parkinson’s disease. In rats, the drug was teratogenic (mainly urogenital defects) at all doses. When it was combined with levodopa/carbidopa or used alone, increased rates of fetal visceral and skeletal defects occurred at all doses studied. In rabbits, given the combination throughout organogenesis, there was an increased incidence of embryo-fetal death and cardiac and skeletal defects. Based on these data, avoiding the drug in pregnancy appears to be the best course.

Valbenazine (Ingrezza) (MW 419) is indicated for the treatment of tardive dyskinesia. The drug caused no malformations in rats and rabbits. However, in rats given the drug during organogenesis through lactation, an increase in the number of stillborn pups and postnatal pup mortalities was observed.

 

Dermatologic

Brodalumab (Siliq) (MW 144,000), given subcutaneously, is indicated for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In monkeys, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from mothers given weekly subcutaneous doses of the drug. Dupilumab (Dupixent) (MW 144,000) is given subcutaneously for the treatment of atopic dermatitis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age.

Guselkumab (Tremfya) (MW 143,600) is given subcutaneously for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age. However, neonatal deaths were observed in three monkeys given six times the maximum recommended human dose.
 

Endocrine/metabolic

Deflazacort (Emflaza) (MW 442) is an oral corticosteroid prodrug indicated for the treatment of Duchenne muscular dystrophy. The drug is converted in vivo to an active metabolite. The drug readily crosses the placenta. Although animal reproduction studies have not been conducted, such studies with other corticosteroids in various animal species have shown an increased incidence of cleft palate. In some species, there was an increase in embryo-fetal death, intrauterine growth restriction, and constriction of the ductus arteriosus.

Ertugliflozin (Steglatro) (MW 566) is an oral drug indicated to improve glycemic control in adults with type 2 diabetes mellitus. In juvenile rats, doses that were about 13 times the human dose caused increased kidney weight, renal tubule and renal pelvis dilatation, and renal mineralization. These effects occurred during periods of rat renal development that correspond to the late second and third trimester of human renal development, and did not fully reverse within a 1-month recovery period. Etelcalcetide (Parsabiv) (MW 1,048), an intravenous calcium-sensing receptor agonist, is indicated for patients on hemodialysis who have secondary hyperparathyroidism. In rats and rabbits given the drug during organogenesis, there was reduced fetal growth. In rats given the drug during organogenesis through birth and weaning, there was a slight increase in pup mortality, delay in parturition, and transient effects on pup growth, but there were no effects on sexual maturation, neurobehavioral, or reproductive function. Macimorelin (Macrilen) (MW 535) is an oral growth hormone secretagogue receptor agonist. It is indicated for adult growth hormone deficiency. Animal reproduction studies have not been conducted.

 

Semaglutide (Ozempic) (MW 4,114), given subcutaneously, is a glucagon-like peptide indicated to improve glycemic control in type 2 diabetes mellitus. In rats given the drug during organogenesis, embryo-fetal death, structural defects, and alterations in growth were observed. In rabbits and monkeys given the drug during organogenesis, there were early pregnancy losses and structural abnormalities. In addition, there was marked maternal body weight loss in both animal species. Vestronidase alfa-vjbk (Mepsevii) is given intravenously. It is indicated for the treatment of Mucopolysaccharidosis VII (Sly syndrome). The calculated average MW of each nonglycosylated peptide chain is 72,562. In rats and rabbits given the drug during organogenesis, there was no maternal toxicity or adverse developmental outcomes.

Gastrointestinal

Plecanatide (Trulance) (MW 1,682) is an oral drug indicated for the treatment of constipation. The drug and its active metabolite are negligibly absorbed systemically and fetal exposure to the drug is not expected. In mice and rabbits given the oral drug during organogenesis, no effects on embryo-fetal development were observed. Telotristat ethyl (Xermelo) (MW 754) is an oral drug indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (MW not specified) therapy in adults not controlled by somatostatin analog. When given during organogenesis in rats, there was no effect on embryo-fetal development at doses that were about nine times the recommended human dose. However, an increased incidence of mortality in rat offspring was observed when the drug was given from organogenesis through lactation. During organogenesis in rabbits, the drug had no embryo-fetal effects at doses that were 10 or more times the human dose.

Hematologics

Betrixaban (Bevyxxa) (MW 568) is an oral factor Xa inhibitor indicated for the prophylaxis of venous thromboembolism. The drug was not associated with adverse developmental fetal outcomes in rats and rabbits. However, maternal hemorrhage did occur. In humans, there is an increased risk of hemorrhage during pregnancy and delivery. Emicizumab (Hemlibra) (MW 145,600), given subcutaneously, is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding in patients with hemophilia A with factor VIII inhibitors. Animal reproduction studies have not been conducted. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta.

 

Immunologic

Sarilumab (Kevzara) (MW 150,000) is given subcutaneously. It is indicated for patients with moderate to severe rheumatoid arthritis. Reproduction studies were conducted in pregnant monkeys. There was no evidence of embryo toxicity or fetal malformations. Based on this data, the human pregnancy risk is low.

 

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508) is a prostaglandin analog that is indicated to reduce intraocular pressure. No quantifiable plasma concentrations of latanoprostene bunod were detected in nonpregnant patients. However, very low levels of latanoprost acid (51-59 pg/mL), the active metabolite, were detected with the maximal plasma concentration occurring 5 minutes after administration. When given intravenously to pregnant rabbits, the drug was shown to be abortifacient and teratogenic, but these effects were not observed in pregnant rats. Netarsudil (Rhopressa) (MW 454) is a kinase inhibitor indicated to reduce intraocular pressure in patients with open-angle glaucoma or ocular hypertension. No quantifiable plasma concentrations of netarsudil were detected in 18 subjects. For the active metabolite, a plasma level of 0.11 ng/mL was found in one subject. Intravenous doses to pregnant rats and rabbits during organogenesis did not cause embryo-fetal adverse effects at clinically relevant systemic exposures.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3,961), given subcutaneously, is a human parathyroid hormone related peptide analog that is indicated for postmenopausal women with osteoporosis at high risk for fracture. Reproduction studies in animals have not been conducted. Because of the indication, it is doubtful if the agent will be used in pregnancy or during breastfeeding.

Respiratory

Benralizumab (Fasenra) (MW 150,000), given subcutaneously, is indicated for the add-on maintenance treatment of severe eosinophilic asthma. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta. Studies in monkeys found no evidence of fetal harm with intravenous doses throughout pregnancy that produced exposures up to about 310 times the exposure at the maximum recommended human dose.

The potential adverse effects in an infant when the mother is taking one of the above drugs while breastfeeding will be covered in my next column.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

 

Novel drugs are innovative new products that have never before been used in clinical practice. Among the 46 that the Food and Drug Administration approved in 2017, 45 could be used in pregnancy. One, cerliponase alfa (Brineura), is indicated for pediatric patients 3 years of age or older, for treatment of late infantile neuronal ceroid lipofuscinosis type 2. It is doubtful that this drug would be used in pregnancy or during breastfeeding.

With the two exceptions noted below, there are no human pregnancy data for these drugs. It is important to consider that although high molecular weight (MW) drugs (for example, greater than 1,000) probably do not usually cross the placenta in the first half of pregnancy, they may do so in late pregnancy. The cited MWs are shown as the nearest whole number. Animal reproductive data are also cited because, although not definitive, they can provide some measure of the human embryo-fetal risk.
 

Anti-infectives

Benznidazole (same trade name) (MW 441), given orally, is indicated for pediatric patients aged 2-12 years for treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi. However, there are international reports describing its use in pregnancy and breastfeeding. No fetal harm from these exposures were noted. Nevertheless, because of the low MW and the reported animal risk, avoiding the drug during the first half of pregnancy appears to be the best choice. Delafloxacin (Baxdela) (MW 441), a fluoroquinolone antimicrobial given intravenously or orally, is indicated for acute bacterial skin infections. The animal data suggest low risk. However, like other fluoroquinolones, it is contraindicated in pregnancy and should be used only if there are no other alternatives.

Glecaprevir/pibrentasvir (Mavyret) (MWs 839, 1,113), a fixed oral dose combination of two antivirals, is indicated for the treatment of hepatitis C virus infection. The animal data suggest low risk. Letermovir (Prevymis) (MW 573) is available for oral and intravenous administration. It is indicated for cytomegalovirus infection. Animal reproduction studies suggest risk. Meropenem/vaborbactam (Vabomere) (MWs 438, 297), given intravenously, is indicated for the treatment of urinary tract infections including pyelonephritis. No malformations were observed in pregnant rats and monkeys exposed to meropenem during organogenesis. Vaborbactam did not cause embryo-fetal harm in rats but did cause a low incidence of malformations in rabbits. Ozenoxacin (Xepi) (MW 363), a cream, is indicated for the topical treatment of impetigo due to Staphylococcus aureus. Among 86 nonpregnant subjects, no systemic absorption was observed in 84, and negligible absorption was observed at the level of detection in 2. Animal reproduction studies were not conducted.

Sofosbuvir/velpatasvir /voxilaprevir (Vosevi) (MWs 529, 883, 869), a fixed oral dose combination of three antivirals, is indicated for the treatment of hepatitis C virus infection. The MWs suggest that all three will cross the human placenta. The animal data suggest low risk. Secnidazole (Solosec) (MW 185), given orally, is indicated for the treatment of bacterial vaginosis. It is closely related to metronidazole. No evidence of embryo-fetal toxicity was observed in rats and rabbits, suggesting that the human risk is low. In a report from Brazil, 134 pregnant women with bacterial vaginosis were treated with secnidazole, metronidazole, or tinidazole in the second and third trimesters. Treatment significantly decreased the incidence of premature rupture of membranes, preterm labor, preterm birth, and low birth weight. No fetal harm was reported.
 

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, in pregnancy and breastfeeding.]

Abemaciclib (Verzenio) (MW 507), an oral inhibitor of cyclin-dependent kinases, is indicated for the treatment of breast cancer. The drug is teratogenic in rats. Acalabrutinib (Calquence) (MW 466) is an oral kinase inhibitor indicated for mantle cell lymphoma. The drug had no effect on the rat embryo-fetus but caused decreased fetal body weights and delayed skeletal ossification in rabbits. Avelumab (Bavencio) (MW 147,000) is given intravenously for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma. Animal reproduction studies have not been conducted. However, based on its mechanism of action, fetal exposure may increase the risk of developing immune-related disorders or altering the normal immune response.

 

Brigatinib (Alunbrig) (MW 584) is given orally for the treatment of metastatic non–small-cell lung cancer. In rats, doses less than or slightly above the human exposure caused multiple anomalies in the fetuses of pregnant rats. Copanlisib (Aliqopa) (MW 553) is a kinase inhibitor that is given intravenously for relapsed follicular lymphoma. In rats during organogenesis, doses based on body surface area that were a fraction of the human dose caused embryo-fetal death and fetal defects. Durvalumab (Imfinzi) (MW 146,000), given intravenously, is indicated for the treatment of metastatic urothelial carcinoma and non–small-cell lung cancer. Monkeys given the drug from organogenesis through delivery experienced increased premature birth, fetal loss, and premature neonatal death. Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose.

Enasidenib (Idhifa) (MW 569), given orally, is indicated for the treatment of myeloid leukemia. The drug caused maternal toxicity and adverse embryo-fetal effects (postimplantation loss, resorptions, decrease viable fetuses, lower fetal birth weights, and skeletal variations) in rats and spontaneous abortions in rabbits. Inotuzumab ozogamicin (Besponsa) (MW 160,000), given intravenously, is indicated for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The drug caused fetal harm in rats but not in rabbits. Midostaurin (Rydapt) (MW 571) is an oral kinase inhibitor indicated for myeloid leukemia. In rats, a dose given during the first week of pregnancy that was a small fraction of the human exposure caused pre- and postimplantation loss. When very small doses were given during organogenesis to rats and rabbits there was significant maternal and fetal toxicity.

Neratinib (Nerlynx) (MW 673) is an oral kinase inhibitor for breast cancer. Although the drug did not cause embryo-fetal toxicity in rats, it did cause this toxicity in rabbits. Doses that resulted in exposures that were less than the human exposure caused maternal toxicity, abortions, and embryo-fetal death. Lower doses caused multiple fetal anomalies. Niraparib (Zejula) (MW 511) is indicated for treatment of epithelial ovarian, fallopian, or peritoneal cancer. Because of the potential human embryo-fetal risk based on its mechanism of action, pregnant animal studies were not conducted. Women with reproductive potential should use effective contraception during treatment and for 6 months after the last dose. Ribociclib (Kisqali) (MW 553) is an oral kinase inhibitor indicated for postmenopausal women with breast cancer. In rats, the drug cause reduced fetal weights and skeletal changes. Increased incidences of fetal abnormalities and lower fetal weights were observed in rabbits.
 

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046) is a naturally occurring peptide hormone given as an intravenous infusion. It is indicated as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. Animal reproduction studies have not been conducted. Because septic or other distributive shock is a medical emergency that can be fatal, the use of this agent in pregnancy should not be withheld.

 

Central nervous system

Deutetrabenazine (Austedo) (MW 324) is an oral drug indicated for the treatment of chorea associated with Huntington’s disease and for tardive dyskinesia. When given to rats during organogenesis there was no clear effect on embryo-fetal development.

Edaravone (Radicava) (MW 174), given as an intravenous infusion, is indicated for the treatment of amyotrophic lateral sclerosis. Doses that were not maternal toxic did not cause embryo-fetal toxicity in rats and rabbits. However, the no-effect dose for developmental toxicity was less than the recommended human dose. Naldemedine (Symproic) (MW 743) is an opioid antagonist indicated for the treatment of opioid-induced constipation. The drug crosses the human placenta and may precipitate opioid withdrawal in the fetus. The drug caused no embryo-fetal adverse effects, even at high doses, in pregnant rats and rabbits.

Ocrelizumab (Ocrevus) (MW 145,000), an intravenous agent, is used to treat patients with multiple sclerosis. The MW is high but immunoglobulins are known to cross the placenta. When given to monkeys at doses similar to or greater than the human dose, there was increased perinatal mortality, depletion of B-cell populations, and renal, bone marrow, and testicular toxicity in the offspring in the absence of maternal toxicity. Safinamide (Xadago) (MW 399) is an oral drug indicated as adjunctive treatment to levodopa/carbidopa in Parkinson’s disease. In rats, the drug was teratogenic (mainly urogenital defects) at all doses. When it was combined with levodopa/carbidopa or used alone, increased rates of fetal visceral and skeletal defects occurred at all doses studied. In rabbits, given the combination throughout organogenesis, there was an increased incidence of embryo-fetal death and cardiac and skeletal defects. Based on these data, avoiding the drug in pregnancy appears to be the best course.

Valbenazine (Ingrezza) (MW 419) is indicated for the treatment of tardive dyskinesia. The drug caused no malformations in rats and rabbits. However, in rats given the drug during organogenesis through lactation, an increase in the number of stillborn pups and postnatal pup mortalities was observed.

 

Dermatologic

Brodalumab (Siliq) (MW 144,000), given subcutaneously, is indicated for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In monkeys, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from mothers given weekly subcutaneous doses of the drug. Dupilumab (Dupixent) (MW 144,000) is given subcutaneously for the treatment of atopic dermatitis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age.

Guselkumab (Tremfya) (MW 143,600) is given subcutaneously for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age. However, neonatal deaths were observed in three monkeys given six times the maximum recommended human dose.
 

Endocrine/metabolic

Deflazacort (Emflaza) (MW 442) is an oral corticosteroid prodrug indicated for the treatment of Duchenne muscular dystrophy. The drug is converted in vivo to an active metabolite. The drug readily crosses the placenta. Although animal reproduction studies have not been conducted, such studies with other corticosteroids in various animal species have shown an increased incidence of cleft palate. In some species, there was an increase in embryo-fetal death, intrauterine growth restriction, and constriction of the ductus arteriosus.

Ertugliflozin (Steglatro) (MW 566) is an oral drug indicated to improve glycemic control in adults with type 2 diabetes mellitus. In juvenile rats, doses that were about 13 times the human dose caused increased kidney weight, renal tubule and renal pelvis dilatation, and renal mineralization. These effects occurred during periods of rat renal development that correspond to the late second and third trimester of human renal development, and did not fully reverse within a 1-month recovery period. Etelcalcetide (Parsabiv) (MW 1,048), an intravenous calcium-sensing receptor agonist, is indicated for patients on hemodialysis who have secondary hyperparathyroidism. In rats and rabbits given the drug during organogenesis, there was reduced fetal growth. In rats given the drug during organogenesis through birth and weaning, there was a slight increase in pup mortality, delay in parturition, and transient effects on pup growth, but there were no effects on sexual maturation, neurobehavioral, or reproductive function. Macimorelin (Macrilen) (MW 535) is an oral growth hormone secretagogue receptor agonist. It is indicated for adult growth hormone deficiency. Animal reproduction studies have not been conducted.

 

Semaglutide (Ozempic) (MW 4,114), given subcutaneously, is a glucagon-like peptide indicated to improve glycemic control in type 2 diabetes mellitus. In rats given the drug during organogenesis, embryo-fetal death, structural defects, and alterations in growth were observed. In rabbits and monkeys given the drug during organogenesis, there were early pregnancy losses and structural abnormalities. In addition, there was marked maternal body weight loss in both animal species. Vestronidase alfa-vjbk (Mepsevii) is given intravenously. It is indicated for the treatment of Mucopolysaccharidosis VII (Sly syndrome). The calculated average MW of each nonglycosylated peptide chain is 72,562. In rats and rabbits given the drug during organogenesis, there was no maternal toxicity or adverse developmental outcomes.

Gastrointestinal

Plecanatide (Trulance) (MW 1,682) is an oral drug indicated for the treatment of constipation. The drug and its active metabolite are negligibly absorbed systemically and fetal exposure to the drug is not expected. In mice and rabbits given the oral drug during organogenesis, no effects on embryo-fetal development were observed. Telotristat ethyl (Xermelo) (MW 754) is an oral drug indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (MW not specified) therapy in adults not controlled by somatostatin analog. When given during organogenesis in rats, there was no effect on embryo-fetal development at doses that were about nine times the recommended human dose. However, an increased incidence of mortality in rat offspring was observed when the drug was given from organogenesis through lactation. During organogenesis in rabbits, the drug had no embryo-fetal effects at doses that were 10 or more times the human dose.

Hematologics

Betrixaban (Bevyxxa) (MW 568) is an oral factor Xa inhibitor indicated for the prophylaxis of venous thromboembolism. The drug was not associated with adverse developmental fetal outcomes in rats and rabbits. However, maternal hemorrhage did occur. In humans, there is an increased risk of hemorrhage during pregnancy and delivery. Emicizumab (Hemlibra) (MW 145,600), given subcutaneously, is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding in patients with hemophilia A with factor VIII inhibitors. Animal reproduction studies have not been conducted. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta.

 

Immunologic

Sarilumab (Kevzara) (MW 150,000) is given subcutaneously. It is indicated for patients with moderate to severe rheumatoid arthritis. Reproduction studies were conducted in pregnant monkeys. There was no evidence of embryo toxicity or fetal malformations. Based on this data, the human pregnancy risk is low.

 

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508) is a prostaglandin analog that is indicated to reduce intraocular pressure. No quantifiable plasma concentrations of latanoprostene bunod were detected in nonpregnant patients. However, very low levels of latanoprost acid (51-59 pg/mL), the active metabolite, were detected with the maximal plasma concentration occurring 5 minutes after administration. When given intravenously to pregnant rabbits, the drug was shown to be abortifacient and teratogenic, but these effects were not observed in pregnant rats. Netarsudil (Rhopressa) (MW 454) is a kinase inhibitor indicated to reduce intraocular pressure in patients with open-angle glaucoma or ocular hypertension. No quantifiable plasma concentrations of netarsudil were detected in 18 subjects. For the active metabolite, a plasma level of 0.11 ng/mL was found in one subject. Intravenous doses to pregnant rats and rabbits during organogenesis did not cause embryo-fetal adverse effects at clinically relevant systemic exposures.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3,961), given subcutaneously, is a human parathyroid hormone related peptide analog that is indicated for postmenopausal women with osteoporosis at high risk for fracture. Reproduction studies in animals have not been conducted. Because of the indication, it is doubtful if the agent will be used in pregnancy or during breastfeeding.

Respiratory

Benralizumab (Fasenra) (MW 150,000), given subcutaneously, is indicated for the add-on maintenance treatment of severe eosinophilic asthma. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta. Studies in monkeys found no evidence of fetal harm with intravenous doses throughout pregnancy that produced exposures up to about 310 times the exposure at the maximum recommended human dose.

The potential adverse effects in an infant when the mother is taking one of the above drugs while breastfeeding will be covered in my next column.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

 

Novel drugs are innovative new products that have never before been used in clinical practice. Among the 46 that the Food and Drug Administration approved in 2017, 45 could be used in pregnancy. One, cerliponase alfa (Brineura), is indicated for pediatric patients 3 years of age or older, for treatment of late infantile neuronal ceroid lipofuscinosis type 2. It is doubtful that this drug would be used in pregnancy or during breastfeeding.

With the two exceptions noted below, there are no human pregnancy data for these drugs. It is important to consider that although high molecular weight (MW) drugs (for example, greater than 1,000) probably do not usually cross the placenta in the first half of pregnancy, they may do so in late pregnancy. The cited MWs are shown as the nearest whole number. Animal reproductive data are also cited because, although not definitive, they can provide some measure of the human embryo-fetal risk.
 

Anti-infectives

Benznidazole (same trade name) (MW 441), given orally, is indicated for pediatric patients aged 2-12 years for treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi. However, there are international reports describing its use in pregnancy and breastfeeding. No fetal harm from these exposures were noted. Nevertheless, because of the low MW and the reported animal risk, avoiding the drug during the first half of pregnancy appears to be the best choice. Delafloxacin (Baxdela) (MW 441), a fluoroquinolone antimicrobial given intravenously or orally, is indicated for acute bacterial skin infections. The animal data suggest low risk. However, like other fluoroquinolones, it is contraindicated in pregnancy and should be used only if there are no other alternatives.

Glecaprevir/pibrentasvir (Mavyret) (MWs 839, 1,113), a fixed oral dose combination of two antivirals, is indicated for the treatment of hepatitis C virus infection. The animal data suggest low risk. Letermovir (Prevymis) (MW 573) is available for oral and intravenous administration. It is indicated for cytomegalovirus infection. Animal reproduction studies suggest risk. Meropenem/vaborbactam (Vabomere) (MWs 438, 297), given intravenously, is indicated for the treatment of urinary tract infections including pyelonephritis. No malformations were observed in pregnant rats and monkeys exposed to meropenem during organogenesis. Vaborbactam did not cause embryo-fetal harm in rats but did cause a low incidence of malformations in rabbits. Ozenoxacin (Xepi) (MW 363), a cream, is indicated for the topical treatment of impetigo due to Staphylococcus aureus. Among 86 nonpregnant subjects, no systemic absorption was observed in 84, and negligible absorption was observed at the level of detection in 2. Animal reproduction studies were not conducted.

Sofosbuvir/velpatasvir /voxilaprevir (Vosevi) (MWs 529, 883, 869), a fixed oral dose combination of three antivirals, is indicated for the treatment of hepatitis C virus infection. The MWs suggest that all three will cross the human placenta. The animal data suggest low risk. Secnidazole (Solosec) (MW 185), given orally, is indicated for the treatment of bacterial vaginosis. It is closely related to metronidazole. No evidence of embryo-fetal toxicity was observed in rats and rabbits, suggesting that the human risk is low. In a report from Brazil, 134 pregnant women with bacterial vaginosis were treated with secnidazole, metronidazole, or tinidazole in the second and third trimesters. Treatment significantly decreased the incidence of premature rupture of membranes, preterm labor, preterm birth, and low birth weight. No fetal harm was reported.
 

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, in pregnancy and breastfeeding.]

Abemaciclib (Verzenio) (MW 507), an oral inhibitor of cyclin-dependent kinases, is indicated for the treatment of breast cancer. The drug is teratogenic in rats. Acalabrutinib (Calquence) (MW 466) is an oral kinase inhibitor indicated for mantle cell lymphoma. The drug had no effect on the rat embryo-fetus but caused decreased fetal body weights and delayed skeletal ossification in rabbits. Avelumab (Bavencio) (MW 147,000) is given intravenously for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma. Animal reproduction studies have not been conducted. However, based on its mechanism of action, fetal exposure may increase the risk of developing immune-related disorders or altering the normal immune response.

 

Brigatinib (Alunbrig) (MW 584) is given orally for the treatment of metastatic non–small-cell lung cancer. In rats, doses less than or slightly above the human exposure caused multiple anomalies in the fetuses of pregnant rats. Copanlisib (Aliqopa) (MW 553) is a kinase inhibitor that is given intravenously for relapsed follicular lymphoma. In rats during organogenesis, doses based on body surface area that were a fraction of the human dose caused embryo-fetal death and fetal defects. Durvalumab (Imfinzi) (MW 146,000), given intravenously, is indicated for the treatment of metastatic urothelial carcinoma and non–small-cell lung cancer. Monkeys given the drug from organogenesis through delivery experienced increased premature birth, fetal loss, and premature neonatal death. Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose.

Enasidenib (Idhifa) (MW 569), given orally, is indicated for the treatment of myeloid leukemia. The drug caused maternal toxicity and adverse embryo-fetal effects (postimplantation loss, resorptions, decrease viable fetuses, lower fetal birth weights, and skeletal variations) in rats and spontaneous abortions in rabbits. Inotuzumab ozogamicin (Besponsa) (MW 160,000), given intravenously, is indicated for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The drug caused fetal harm in rats but not in rabbits. Midostaurin (Rydapt) (MW 571) is an oral kinase inhibitor indicated for myeloid leukemia. In rats, a dose given during the first week of pregnancy that was a small fraction of the human exposure caused pre- and postimplantation loss. When very small doses were given during organogenesis to rats and rabbits there was significant maternal and fetal toxicity.

Neratinib (Nerlynx) (MW 673) is an oral kinase inhibitor for breast cancer. Although the drug did not cause embryo-fetal toxicity in rats, it did cause this toxicity in rabbits. Doses that resulted in exposures that were less than the human exposure caused maternal toxicity, abortions, and embryo-fetal death. Lower doses caused multiple fetal anomalies. Niraparib (Zejula) (MW 511) is indicated for treatment of epithelial ovarian, fallopian, or peritoneal cancer. Because of the potential human embryo-fetal risk based on its mechanism of action, pregnant animal studies were not conducted. Women with reproductive potential should use effective contraception during treatment and for 6 months after the last dose. Ribociclib (Kisqali) (MW 553) is an oral kinase inhibitor indicated for postmenopausal women with breast cancer. In rats, the drug cause reduced fetal weights and skeletal changes. Increased incidences of fetal abnormalities and lower fetal weights were observed in rabbits.
 

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046) is a naturally occurring peptide hormone given as an intravenous infusion. It is indicated as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. Animal reproduction studies have not been conducted. Because septic or other distributive shock is a medical emergency that can be fatal, the use of this agent in pregnancy should not be withheld.

 

Central nervous system

Deutetrabenazine (Austedo) (MW 324) is an oral drug indicated for the treatment of chorea associated with Huntington’s disease and for tardive dyskinesia. When given to rats during organogenesis there was no clear effect on embryo-fetal development.

Edaravone (Radicava) (MW 174), given as an intravenous infusion, is indicated for the treatment of amyotrophic lateral sclerosis. Doses that were not maternal toxic did not cause embryo-fetal toxicity in rats and rabbits. However, the no-effect dose for developmental toxicity was less than the recommended human dose. Naldemedine (Symproic) (MW 743) is an opioid antagonist indicated for the treatment of opioid-induced constipation. The drug crosses the human placenta and may precipitate opioid withdrawal in the fetus. The drug caused no embryo-fetal adverse effects, even at high doses, in pregnant rats and rabbits.

Ocrelizumab (Ocrevus) (MW 145,000), an intravenous agent, is used to treat patients with multiple sclerosis. The MW is high but immunoglobulins are known to cross the placenta. When given to monkeys at doses similar to or greater than the human dose, there was increased perinatal mortality, depletion of B-cell populations, and renal, bone marrow, and testicular toxicity in the offspring in the absence of maternal toxicity. Safinamide (Xadago) (MW 399) is an oral drug indicated as adjunctive treatment to levodopa/carbidopa in Parkinson’s disease. In rats, the drug was teratogenic (mainly urogenital defects) at all doses. When it was combined with levodopa/carbidopa or used alone, increased rates of fetal visceral and skeletal defects occurred at all doses studied. In rabbits, given the combination throughout organogenesis, there was an increased incidence of embryo-fetal death and cardiac and skeletal defects. Based on these data, avoiding the drug in pregnancy appears to be the best course.

Valbenazine (Ingrezza) (MW 419) is indicated for the treatment of tardive dyskinesia. The drug caused no malformations in rats and rabbits. However, in rats given the drug during organogenesis through lactation, an increase in the number of stillborn pups and postnatal pup mortalities was observed.

 

Dermatologic

Brodalumab (Siliq) (MW 144,000), given subcutaneously, is indicated for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In monkeys, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from mothers given weekly subcutaneous doses of the drug. Dupilumab (Dupixent) (MW 144,000) is given subcutaneously for the treatment of atopic dermatitis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age.

Guselkumab (Tremfya) (MW 143,600) is given subcutaneously for the treatment of moderate to severe plaque psoriasis. It is a human monoclonal IgG antibody and, even though the MW is high, IgG antibodies are known to cross the placenta. In pregnant monkeys given subcutaneous doses of the drug, no drug-related effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from birth to 6 months of age. However, neonatal deaths were observed in three monkeys given six times the maximum recommended human dose.
 

Endocrine/metabolic

Deflazacort (Emflaza) (MW 442) is an oral corticosteroid prodrug indicated for the treatment of Duchenne muscular dystrophy. The drug is converted in vivo to an active metabolite. The drug readily crosses the placenta. Although animal reproduction studies have not been conducted, such studies with other corticosteroids in various animal species have shown an increased incidence of cleft palate. In some species, there was an increase in embryo-fetal death, intrauterine growth restriction, and constriction of the ductus arteriosus.

Ertugliflozin (Steglatro) (MW 566) is an oral drug indicated to improve glycemic control in adults with type 2 diabetes mellitus. In juvenile rats, doses that were about 13 times the human dose caused increased kidney weight, renal tubule and renal pelvis dilatation, and renal mineralization. These effects occurred during periods of rat renal development that correspond to the late second and third trimester of human renal development, and did not fully reverse within a 1-month recovery period. Etelcalcetide (Parsabiv) (MW 1,048), an intravenous calcium-sensing receptor agonist, is indicated for patients on hemodialysis who have secondary hyperparathyroidism. In rats and rabbits given the drug during organogenesis, there was reduced fetal growth. In rats given the drug during organogenesis through birth and weaning, there was a slight increase in pup mortality, delay in parturition, and transient effects on pup growth, but there were no effects on sexual maturation, neurobehavioral, or reproductive function. Macimorelin (Macrilen) (MW 535) is an oral growth hormone secretagogue receptor agonist. It is indicated for adult growth hormone deficiency. Animal reproduction studies have not been conducted.

 

Semaglutide (Ozempic) (MW 4,114), given subcutaneously, is a glucagon-like peptide indicated to improve glycemic control in type 2 diabetes mellitus. In rats given the drug during organogenesis, embryo-fetal death, structural defects, and alterations in growth were observed. In rabbits and monkeys given the drug during organogenesis, there were early pregnancy losses and structural abnormalities. In addition, there was marked maternal body weight loss in both animal species. Vestronidase alfa-vjbk (Mepsevii) is given intravenously. It is indicated for the treatment of Mucopolysaccharidosis VII (Sly syndrome). The calculated average MW of each nonglycosylated peptide chain is 72,562. In rats and rabbits given the drug during organogenesis, there was no maternal toxicity or adverse developmental outcomes.

Gastrointestinal

Plecanatide (Trulance) (MW 1,682) is an oral drug indicated for the treatment of constipation. The drug and its active metabolite are negligibly absorbed systemically and fetal exposure to the drug is not expected. In mice and rabbits given the oral drug during organogenesis, no effects on embryo-fetal development were observed. Telotristat ethyl (Xermelo) (MW 754) is an oral drug indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (MW not specified) therapy in adults not controlled by somatostatin analog. When given during organogenesis in rats, there was no effect on embryo-fetal development at doses that were about nine times the recommended human dose. However, an increased incidence of mortality in rat offspring was observed when the drug was given from organogenesis through lactation. During organogenesis in rabbits, the drug had no embryo-fetal effects at doses that were 10 or more times the human dose.

Hematologics

Betrixaban (Bevyxxa) (MW 568) is an oral factor Xa inhibitor indicated for the prophylaxis of venous thromboembolism. The drug was not associated with adverse developmental fetal outcomes in rats and rabbits. However, maternal hemorrhage did occur. In humans, there is an increased risk of hemorrhage during pregnancy and delivery. Emicizumab (Hemlibra) (MW 145,600), given subcutaneously, is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding in patients with hemophilia A with factor VIII inhibitors. Animal reproduction studies have not been conducted. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta.

 

Immunologic

Sarilumab (Kevzara) (MW 150,000) is given subcutaneously. It is indicated for patients with moderate to severe rheumatoid arthritis. Reproduction studies were conducted in pregnant monkeys. There was no evidence of embryo toxicity or fetal malformations. Based on this data, the human pregnancy risk is low.

 

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508) is a prostaglandin analog that is indicated to reduce intraocular pressure. No quantifiable plasma concentrations of latanoprostene bunod were detected in nonpregnant patients. However, very low levels of latanoprost acid (51-59 pg/mL), the active metabolite, were detected with the maximal plasma concentration occurring 5 minutes after administration. When given intravenously to pregnant rabbits, the drug was shown to be abortifacient and teratogenic, but these effects were not observed in pregnant rats. Netarsudil (Rhopressa) (MW 454) is a kinase inhibitor indicated to reduce intraocular pressure in patients with open-angle glaucoma or ocular hypertension. No quantifiable plasma concentrations of netarsudil were detected in 18 subjects. For the active metabolite, a plasma level of 0.11 ng/mL was found in one subject. Intravenous doses to pregnant rats and rabbits during organogenesis did not cause embryo-fetal adverse effects at clinically relevant systemic exposures.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3,961), given subcutaneously, is a human parathyroid hormone related peptide analog that is indicated for postmenopausal women with osteoporosis at high risk for fracture. Reproduction studies in animals have not been conducted. Because of the indication, it is doubtful if the agent will be used in pregnancy or during breastfeeding.

Respiratory

Benralizumab (Fasenra) (MW 150,000), given subcutaneously, is indicated for the add-on maintenance treatment of severe eosinophilic asthma. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta. Studies in monkeys found no evidence of fetal harm with intravenous doses throughout pregnancy that produced exposures up to about 310 times the exposure at the maximum recommended human dose.

The potential adverse effects in an infant when the mother is taking one of the above drugs while breastfeeding will be covered in my next column.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

 

A transition is coming. My fourth and final year of residency starts soon – meaning that from July 1, 2018, I’ll never again be on call overnight as a psychiatry resident. July 1 marks the end of 2 years as a PGY2 and PGY3, during which I’ve worked 60 overnight shifts.

In our residency program, the on-call shift is a continuation of daytime duties, and the experience is a formative physician-in-training/quasi-hazing process of care provision for 24 hours straight. Previously, I’ve recounted experiences from my overnight on-call shifts and reflected on the intensity of working with emotionally distressed individuals in the emergency department. I never thought I’d say it, but I will miss working in the middle of the night, particularly in the ED. In the small hours of the morning, the strange aura of hospital existence, and desperation of sickness isn’t washed out by daylight and the inhibitions of business hours.

Thomas Northcut/Thinkstock

Being on call is a fact of medical training. No doubt it makes us stronger, more experienced physicians, able to respond to challenging clinical experiences in a less-than-optimal environment. But that doesn’t mean it isn’t painful.

As part of yearlong monitoring research, I’ve asked my fellow residents at George Washington University, in Washington, to participate in a quality improvement survey. It collects information on the number of patients evaluated overnight while on call and also asks residents to rate their on-call experiences on an “emotional pain scale” with space for a qualitative comment. The emotional pain scale is a simple visual analog scale for pain, with a smiley face representing 0 pain and the sad face with tears representing the 10 out of 10, worst pain imaginable. Initially, the emotional pain scale seemed a lighthearted and somewhat silly way for residents to vent about their on-call experience. A year of data collection later, I consider the emotional pain scale an important acknowledgment to my fellow residents that being on call is physically and emotionally taxing.

At the 2018 American Psychiatric Association meeting in New York, I presented findings from this survey data, examining the quantitative information showing that sheer volume of patients correlates with higher emotional pain scores. But while compiling and analyzing the data for my presentation, I also found myself reading and rereading the comments left by my colleagues about their hardest nights. As I read, I reflected on my own 60 nights on call, and my personal experiences between the highs and lows of emotional pain.

As an homage to the educational and emotional power of being on call, I’d like to share a few vignettes from my years of overnight calls from across the emotional pain scale. (Key demographic details have been omitted to protect patients’ privacy.):

• 0: There is no such thing as 0 emotional pain when asked to stay overnight in the hospital.

 

• 1: This is a full night of sleep on the uncomfortable bunk beds in the GWU call room. On occasion, I’ve had a night with one consult. Only once in 2 years did I have a night in which not a single consult was called from the ED and all the patients on the psychiatric unit slept as soundly as I did.
• 4: There’s a man I’ve seen in the ED seven times over the last 2 years. That’s more than 10% of my nights on call, so we’re well acquainted – though he has trouble remembering me. He’s an alcoholic, though I know the official diagnosis is alcohol use disorder–severe. His addiction is, indeed, severe; I’ve never seen him sober. Every time, he tells me how his wife is cheating on him, and he’s been depressed since his eldest son was killed in a shooting 10 years ago. He sits under a bridge and drinks liquor until he either goes home or to an ED. I feel for him. Several times, other residents and I have transferred him to a local detoxification unit with discharge to a 30-day drug rehab program. It doesn’t stick. The last time I evaluated him, I sent him home to his wife with a cab voucher. My emotional pain is equal parts pity and frustration over my ineffectual impact on his life. He, and others like him, used to cause me more emotional pain. Eventually, the pain is dulled.

  

• 5: The mean pain scale score of a GWU resident on call is 5.13. Analysis of the survey data showed the emotional pain score is correlated with the specific resident on call, and my personal average is 5.04. From the way residents talk about being on call, I expected the mean pain scale to be higher. There is no vignette for the mean score; I think of it as all the unremarkable calls blurred together.
• 8: Emotional pain rises with a fraught clinical scenario. One weeknight, I had to involuntarily commit a young lawyer who was psychotic yet adept at hiding it. The lawyer was brought into the ED by police after his brother in Chicago called them to his apartment. The patient had called the brother while standing on his 10th-floor balcony talking nonsensically about conspiracy theories and why he needed to end his life to save the world. In the ED, the patient denied every single part of the story. When I called the brother for collateral, his distress moved me as a both sibling and psychiatrist. The lawyer denied the story up and down, called his brother a liar and the favorite child, and refused to sign into the psychiatric hospital voluntarily. I felt I had no choice but to place him in an involuntary hold. It was a long and busy night, and every time I walked past his ED bay, he’d yell, “Is this the face of a crazy man? I know the law!” I tried to put myself in his position and that of his brother who had called the police. Eight is the emotional pain of involuntarily committing someone whose story isn’t black and white. Eight is the pain of exercising authority and beneficence over patient autonomy.

 

• 10: I was consulted to evaluate a woman for suicidal ideation whose mother had coded and died in the ED an hour before. When the woman was told of her mother’s death, she crumpled to floor, screaming she wanted to die to join her mother. In the tumult, ED staff thought she was running out of the hospital to jump into traffic. She was held in the ED involuntarily until she could be evaluated for safety by psychiatry – me. When I entered her hospital room, she was quietly weeping, whispering: “I want my mom. I want my mom.” I wanted to cry, too. I sat with her in silence for a few minutes and offered my condolences. Yet, as the consultant, I had a job to do: I needed to complete a risk assessment. My voice caught as I explained that I was here to assess her for suicidal thoughts and plans. She looked at me like I was crazy. I felt crazy. I acknowledged the risk of suicide and her expressed desire to join her mother in death. I asked the questions quickly and gently. She shook her head to all my questions and told me she just wanted to go home. I met her daughters in the waiting room who were caught up in grief over the combination of their grandmother’s death and their mother’s reaction. They seemed certain that their mother had not wanted to die, and we agreed it was a situation of the wrong reaction in the wrong place. The daughters agreed to take her home and watch her all night. This is the only 10 I’ve experienced on the emotional pain scale. I felt shame and confusion as I struggled to reconcile my obligation as a psychiatrist, and my true desire to give that woman a hug and send her home without a battery of questions at perhaps her most vulnerable moment.

Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at GWU. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.

 

A transition is coming. My fourth and final year of residency starts soon – meaning that from July 1, 2018, I’ll never again be on call overnight as a psychiatry resident. July 1 marks the end of 2 years as a PGY2 and PGY3, during which I’ve worked 60 overnight shifts.

In our residency program, the on-call shift is a continuation of daytime duties, and the experience is a formative physician-in-training/quasi-hazing process of care provision for 24 hours straight. Previously, I’ve recounted experiences from my overnight on-call shifts and reflected on the intensity of working with emotionally distressed individuals in the emergency department. I never thought I’d say it, but I will miss working in the middle of the night, particularly in the ED. In the small hours of the morning, the strange aura of hospital existence, and desperation of sickness isn’t washed out by daylight and the inhibitions of business hours.

Thomas Northcut/Thinkstock

Being on call is a fact of medical training. No doubt it makes us stronger, more experienced physicians, able to respond to challenging clinical experiences in a less-than-optimal environment. But that doesn’t mean it isn’t painful.

As part of yearlong monitoring research, I’ve asked my fellow residents at George Washington University, in Washington, to participate in a quality improvement survey. It collects information on the number of patients evaluated overnight while on call and also asks residents to rate their on-call experiences on an “emotional pain scale” with space for a qualitative comment. The emotional pain scale is a simple visual analog scale for pain, with a smiley face representing 0 pain and the sad face with tears representing the 10 out of 10, worst pain imaginable. Initially, the emotional pain scale seemed a lighthearted and somewhat silly way for residents to vent about their on-call experience. A year of data collection later, I consider the emotional pain scale an important acknowledgment to my fellow residents that being on call is physically and emotionally taxing.

At the 2018 American Psychiatric Association meeting in New York, I presented findings from this survey data, examining the quantitative information showing that sheer volume of patients correlates with higher emotional pain scores. But while compiling and analyzing the data for my presentation, I also found myself reading and rereading the comments left by my colleagues about their hardest nights. As I read, I reflected on my own 60 nights on call, and my personal experiences between the highs and lows of emotional pain.

As an homage to the educational and emotional power of being on call, I’d like to share a few vignettes from my years of overnight calls from across the emotional pain scale. (Key demographic details have been omitted to protect patients’ privacy.):

• 0: There is no such thing as 0 emotional pain when asked to stay overnight in the hospital.

 

• 1: This is a full night of sleep on the uncomfortable bunk beds in the GWU call room. On occasion, I’ve had a night with one consult. Only once in 2 years did I have a night in which not a single consult was called from the ED and all the patients on the psychiatric unit slept as soundly as I did.
• 4: There’s a man I’ve seen in the ED seven times over the last 2 years. That’s more than 10% of my nights on call, so we’re well acquainted – though he has trouble remembering me. He’s an alcoholic, though I know the official diagnosis is alcohol use disorder–severe. His addiction is, indeed, severe; I’ve never seen him sober. Every time, he tells me how his wife is cheating on him, and he’s been depressed since his eldest son was killed in a shooting 10 years ago. He sits under a bridge and drinks liquor until he either goes home or to an ED. I feel for him. Several times, other residents and I have transferred him to a local detoxification unit with discharge to a 30-day drug rehab program. It doesn’t stick. The last time I evaluated him, I sent him home to his wife with a cab voucher. My emotional pain is equal parts pity and frustration over my ineffectual impact on his life. He, and others like him, used to cause me more emotional pain. Eventually, the pain is dulled.

  

• 5: The mean pain scale score of a GWU resident on call is 5.13. Analysis of the survey data showed the emotional pain score is correlated with the specific resident on call, and my personal average is 5.04. From the way residents talk about being on call, I expected the mean pain scale to be higher. There is no vignette for the mean score; I think of it as all the unremarkable calls blurred together.
• 8: Emotional pain rises with a fraught clinical scenario. One weeknight, I had to involuntarily commit a young lawyer who was psychotic yet adept at hiding it. The lawyer was brought into the ED by police after his brother in Chicago called them to his apartment. The patient had called the brother while standing on his 10th-floor balcony talking nonsensically about conspiracy theories and why he needed to end his life to save the world. In the ED, the patient denied every single part of the story. When I called the brother for collateral, his distress moved me as a both sibling and psychiatrist. The lawyer denied the story up and down, called his brother a liar and the favorite child, and refused to sign into the psychiatric hospital voluntarily. I felt I had no choice but to place him in an involuntary hold. It was a long and busy night, and every time I walked past his ED bay, he’d yell, “Is this the face of a crazy man? I know the law!” I tried to put myself in his position and that of his brother who had called the police. Eight is the emotional pain of involuntarily committing someone whose story isn’t black and white. Eight is the pain of exercising authority and beneficence over patient autonomy.

 

• 10: I was consulted to evaluate a woman for suicidal ideation whose mother had coded and died in the ED an hour before. When the woman was told of her mother’s death, she crumpled to floor, screaming she wanted to die to join her mother. In the tumult, ED staff thought she was running out of the hospital to jump into traffic. She was held in the ED involuntarily until she could be evaluated for safety by psychiatry – me. When I entered her hospital room, she was quietly weeping, whispering: “I want my mom. I want my mom.” I wanted to cry, too. I sat with her in silence for a few minutes and offered my condolences. Yet, as the consultant, I had a job to do: I needed to complete a risk assessment. My voice caught as I explained that I was here to assess her for suicidal thoughts and plans. She looked at me like I was crazy. I felt crazy. I acknowledged the risk of suicide and her expressed desire to join her mother in death. I asked the questions quickly and gently. She shook her head to all my questions and told me she just wanted to go home. I met her daughters in the waiting room who were caught up in grief over the combination of their grandmother’s death and their mother’s reaction. They seemed certain that their mother had not wanted to die, and we agreed it was a situation of the wrong reaction in the wrong place. The daughters agreed to take her home and watch her all night. This is the only 10 I’ve experienced on the emotional pain scale. I felt shame and confusion as I struggled to reconcile my obligation as a psychiatrist, and my true desire to give that woman a hug and send her home without a battery of questions at perhaps her most vulnerable moment.

Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at GWU. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.

 

A transition is coming. My fourth and final year of residency starts soon – meaning that from July 1, 2018, I’ll never again be on call overnight as a psychiatry resident. July 1 marks the end of 2 years as a PGY2 and PGY3, during which I’ve worked 60 overnight shifts.

In our residency program, the on-call shift is a continuation of daytime duties, and the experience is a formative physician-in-training/quasi-hazing process of care provision for 24 hours straight. Previously, I’ve recounted experiences from my overnight on-call shifts and reflected on the intensity of working with emotionally distressed individuals in the emergency department. I never thought I’d say it, but I will miss working in the middle of the night, particularly in the ED. In the small hours of the morning, the strange aura of hospital existence, and desperation of sickness isn’t washed out by daylight and the inhibitions of business hours.

Thomas Northcut/Thinkstock

Being on call is a fact of medical training. No doubt it makes us stronger, more experienced physicians, able to respond to challenging clinical experiences in a less-than-optimal environment. But that doesn’t mean it isn’t painful.

As part of yearlong monitoring research, I’ve asked my fellow residents at George Washington University, in Washington, to participate in a quality improvement survey. It collects information on the number of patients evaluated overnight while on call and also asks residents to rate their on-call experiences on an “emotional pain scale” with space for a qualitative comment. The emotional pain scale is a simple visual analog scale for pain, with a smiley face representing 0 pain and the sad face with tears representing the 10 out of 10, worst pain imaginable. Initially, the emotional pain scale seemed a lighthearted and somewhat silly way for residents to vent about their on-call experience. A year of data collection later, I consider the emotional pain scale an important acknowledgment to my fellow residents that being on call is physically and emotionally taxing.

At the 2018 American Psychiatric Association meeting in New York, I presented findings from this survey data, examining the quantitative information showing that sheer volume of patients correlates with higher emotional pain scores. But while compiling and analyzing the data for my presentation, I also found myself reading and rereading the comments left by my colleagues about their hardest nights. As I read, I reflected on my own 60 nights on call, and my personal experiences between the highs and lows of emotional pain.

As an homage to the educational and emotional power of being on call, I’d like to share a few vignettes from my years of overnight calls from across the emotional pain scale. (Key demographic details have been omitted to protect patients’ privacy.):

• 0: There is no such thing as 0 emotional pain when asked to stay overnight in the hospital.

 

• 1: This is a full night of sleep on the uncomfortable bunk beds in the GWU call room. On occasion, I’ve had a night with one consult. Only once in 2 years did I have a night in which not a single consult was called from the ED and all the patients on the psychiatric unit slept as soundly as I did.
• 4: There’s a man I’ve seen in the ED seven times over the last 2 years. That’s more than 10% of my nights on call, so we’re well acquainted – though he has trouble remembering me. He’s an alcoholic, though I know the official diagnosis is alcohol use disorder–severe. His addiction is, indeed, severe; I’ve never seen him sober. Every time, he tells me how his wife is cheating on him, and he’s been depressed since his eldest son was killed in a shooting 10 years ago. He sits under a bridge and drinks liquor until he either goes home or to an ED. I feel for him. Several times, other residents and I have transferred him to a local detoxification unit with discharge to a 30-day drug rehab program. It doesn’t stick. The last time I evaluated him, I sent him home to his wife with a cab voucher. My emotional pain is equal parts pity and frustration over my ineffectual impact on his life. He, and others like him, used to cause me more emotional pain. Eventually, the pain is dulled.

  

• 5: The mean pain scale score of a GWU resident on call is 5.13. Analysis of the survey data showed the emotional pain score is correlated with the specific resident on call, and my personal average is 5.04. From the way residents talk about being on call, I expected the mean pain scale to be higher. There is no vignette for the mean score; I think of it as all the unremarkable calls blurred together.
• 8: Emotional pain rises with a fraught clinical scenario. One weeknight, I had to involuntarily commit a young lawyer who was psychotic yet adept at hiding it. The lawyer was brought into the ED by police after his brother in Chicago called them to his apartment. The patient had called the brother while standing on his 10th-floor balcony talking nonsensically about conspiracy theories and why he needed to end his life to save the world. In the ED, the patient denied every single part of the story. When I called the brother for collateral, his distress moved me as a both sibling and psychiatrist. The lawyer denied the story up and down, called his brother a liar and the favorite child, and refused to sign into the psychiatric hospital voluntarily. I felt I had no choice but to place him in an involuntary hold. It was a long and busy night, and every time I walked past his ED bay, he’d yell, “Is this the face of a crazy man? I know the law!” I tried to put myself in his position and that of his brother who had called the police. Eight is the emotional pain of involuntarily committing someone whose story isn’t black and white. Eight is the pain of exercising authority and beneficence over patient autonomy.

 

• 10: I was consulted to evaluate a woman for suicidal ideation whose mother had coded and died in the ED an hour before. When the woman was told of her mother’s death, she crumpled to floor, screaming she wanted to die to join her mother. In the tumult, ED staff thought she was running out of the hospital to jump into traffic. She was held in the ED involuntarily until she could be evaluated for safety by psychiatry – me. When I entered her hospital room, she was quietly weeping, whispering: “I want my mom. I want my mom.” I wanted to cry, too. I sat with her in silence for a few minutes and offered my condolences. Yet, as the consultant, I had a job to do: I needed to complete a risk assessment. My voice caught as I explained that I was here to assess her for suicidal thoughts and plans. She looked at me like I was crazy. I felt crazy. I acknowledged the risk of suicide and her expressed desire to join her mother in death. I asked the questions quickly and gently. She shook her head to all my questions and told me she just wanted to go home. I met her daughters in the waiting room who were caught up in grief over the combination of their grandmother’s death and their mother’s reaction. They seemed certain that their mother had not wanted to die, and we agreed it was a situation of the wrong reaction in the wrong place. The daughters agreed to take her home and watch her all night. This is the only 10 I’ve experienced on the emotional pain scale. I felt shame and confusion as I struggled to reconcile my obligation as a psychiatrist, and my true desire to give that woman a hug and send her home without a battery of questions at perhaps her most vulnerable moment.

Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at GWU. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.

 

The emergency department locum tenens staff recruiter was persuasive. “It’s a quiet little ER where you can study and sleep.” I was board certified in internal medicine and had trained in a busy urban emergency department. This was just the spot to make a little folding money and study for my mock dermatology boards, I thought.

And so, on a Saturday night in rural Texas, after grinding rust out of a pipe fitter’s eye and stitching up two brawlers from the local biker bar, I was faced with treating a comatose kid brought in after a car crash. He had not been wearing a seat belt, and his car had rolled over on his head.

I was way over my skill level, but I was lucky. I was able to stabilize him and, after several long hours, I got him on an emergency helicopter into Dallas.

But the experience changed me. I realized I did not know enough to deal with this case on my own. After making it through that night in the ED, I never put myself in that position again.

I now knew what I did not know.

A study recently published in JAMA Dermatology reminded me of that experience in Texas. The study compared the accuracy of skin cancer diagnoses by physician assistants (PAs) and dermatologists for about 20,000 patients and 33,000 patient encounters for skin cancer screening between January 2011 and December 2015 at dermatology offices affiliated with the University of Pittsburgh. No significant differences in diagnoses of nonmelanoma skin cancer and invasive melanoma were found.

The finding that jumped out to me, though, was that patients screened by a PA were significantly less likely to be diagnosed with melanoma in situ, the stage when melanoma is 100% curable. Yet, those patients screened by PAs underwent a lot more skin biopsies – 36% more skin biopsies per melanoma in situ diagnosed, compared with patients of dermatologists. Interestingly, in the health care system studied, any PA with a question about a patient can ask an attending dermatologist to see the patient. Did that factor account for the diagnostic comparability for nonmelanoma skin cancer and invasive melanoma? Did the PAs not ask for help on the missed melanomas in situ? If so, I believe this may be a situation of PAs not knowing what they didn’t know.

 

Now a knowledgeable friend of mine thinks this study is biased because 17% more patients with prior melanomas were seen by a dermatologist rather than by a PA. While it’s true that patients with prior melanomas are more likely to develop new melanomas, the counterargument is that the bar for a biopsy in a patient with a prior melanoma is much lower. Patients with a history of melanoma should have more skin biopsies, but the dermatologists in this study still took many fewer biopsies to diagnose melanomas in situ.

Why do these findings matter for patients and for the health care system?

PAs billed independently for 12% of skin biopsies (including lip, ear, ear canal, vulva, penis, and eyelid) in Medicare Fee for Service in 2016. Skin biopsies paid for by Medicare have been increasing at a very rapid rate, about twice as fast as the rate reflected in the current skin cancer epidemic.

Every skin biopsy results in a pathology charge, for which Medicare pays about $70. A level 3 new patient visit pays $110. If PAs bill independently, they are paid at 85% of the fee schedule, which often is touted as a great savings. Therefore, if only 24.2% of skin biopsies by PAs were unnecessary, even at a reduced 85% reimbursement, it costs Medicare more than having these visits and biopsies provided by a dermatologist. The cost savings decrease even more with additional skin biopsies, because they pay so little ($33 for a doctor, $28 for a PA), yet the pathology charge is unchanged.

 

There are other costs beyond monetary ones from unnecessary skin biopsies: scarring, follow-up procedures for uncertain diagnoses such as mild dysplastic nevi, ambiguous results, and emotional angst to patients.

Further, three new skin biopsy CPT codes have recently been surveyed by the Relative Value Scale Update Committee, which means that the increasing number of skin biopsies has triggered a review. This is not good news.Dermatology appears simple and easy, but in fact it is not. While less dramatic than a closed head injury, a missed melanoma in situ can be just as deadly. It is hard to know when you do not know something.

If the results of this large study are to be believed, many melanomas in situ are going to be missed if PAs perform unsupervised skin cancer screenings. This is not a tenable proposition, ethically or legally. Dermatologists and PAs need to work together to ensure this does not happen.

An estimated 2,520 dermatology PAs were practicing in the United States in 2016, based on membership data from the Society of Dermatology PAs (SDPA), according to a research letter published last year (J Am Acad Dermatol. 2017 Jun;76[6]:1200-2). The SDPA, as stated in an SDPA position statement published in the winter 2017 newsletter, hopes to gain access to direct billing to public and private insurers, which would include the Centers for Medicare & Medicaid Services, and for PAs to no longer report to other health care professionals.

 

Many dermatologists, as well as teaching programs, use PAs to perform skin cancer screenings, sometimes unsupervised, which makes diagnostic accuracy critical. The issues at hand are the safety of patients and the accuracy of diagnosis as well as the costs to the health care system. A team effort, which includes direct supervision, is needed to ensure those issues are addressed.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

 

The emergency department locum tenens staff recruiter was persuasive. “It’s a quiet little ER where you can study and sleep.” I was board certified in internal medicine and had trained in a busy urban emergency department. This was just the spot to make a little folding money and study for my mock dermatology boards, I thought.

And so, on a Saturday night in rural Texas, after grinding rust out of a pipe fitter’s eye and stitching up two brawlers from the local biker bar, I was faced with treating a comatose kid brought in after a car crash. He had not been wearing a seat belt, and his car had rolled over on his head.

I was way over my skill level, but I was lucky. I was able to stabilize him and, after several long hours, I got him on an emergency helicopter into Dallas.

But the experience changed me. I realized I did not know enough to deal with this case on my own. After making it through that night in the ED, I never put myself in that position again.

I now knew what I did not know.

A study recently published in JAMA Dermatology reminded me of that experience in Texas. The study compared the accuracy of skin cancer diagnoses by physician assistants (PAs) and dermatologists for about 20,000 patients and 33,000 patient encounters for skin cancer screening between January 2011 and December 2015 at dermatology offices affiliated with the University of Pittsburgh. No significant differences in diagnoses of nonmelanoma skin cancer and invasive melanoma were found.

The finding that jumped out to me, though, was that patients screened by a PA were significantly less likely to be diagnosed with melanoma in situ, the stage when melanoma is 100% curable. Yet, those patients screened by PAs underwent a lot more skin biopsies – 36% more skin biopsies per melanoma in situ diagnosed, compared with patients of dermatologists. Interestingly, in the health care system studied, any PA with a question about a patient can ask an attending dermatologist to see the patient. Did that factor account for the diagnostic comparability for nonmelanoma skin cancer and invasive melanoma? Did the PAs not ask for help on the missed melanomas in situ? If so, I believe this may be a situation of PAs not knowing what they didn’t know.

 

Now a knowledgeable friend of mine thinks this study is biased because 17% more patients with prior melanomas were seen by a dermatologist rather than by a PA. While it’s true that patients with prior melanomas are more likely to develop new melanomas, the counterargument is that the bar for a biopsy in a patient with a prior melanoma is much lower. Patients with a history of melanoma should have more skin biopsies, but the dermatologists in this study still took many fewer biopsies to diagnose melanomas in situ.

Why do these findings matter for patients and for the health care system?

PAs billed independently for 12% of skin biopsies (including lip, ear, ear canal, vulva, penis, and eyelid) in Medicare Fee for Service in 2016. Skin biopsies paid for by Medicare have been increasing at a very rapid rate, about twice as fast as the rate reflected in the current skin cancer epidemic.

Every skin biopsy results in a pathology charge, for which Medicare pays about $70. A level 3 new patient visit pays $110. If PAs bill independently, they are paid at 85% of the fee schedule, which often is touted as a great savings. Therefore, if only 24.2% of skin biopsies by PAs were unnecessary, even at a reduced 85% reimbursement, it costs Medicare more than having these visits and biopsies provided by a dermatologist. The cost savings decrease even more with additional skin biopsies, because they pay so little ($33 for a doctor, $28 for a PA), yet the pathology charge is unchanged.

 

There are other costs beyond monetary ones from unnecessary skin biopsies: scarring, follow-up procedures for uncertain diagnoses such as mild dysplastic nevi, ambiguous results, and emotional angst to patients.

Further, three new skin biopsy CPT codes have recently been surveyed by the Relative Value Scale Update Committee, which means that the increasing number of skin biopsies has triggered a review. This is not good news.Dermatology appears simple and easy, but in fact it is not. While less dramatic than a closed head injury, a missed melanoma in situ can be just as deadly. It is hard to know when you do not know something.

If the results of this large study are to be believed, many melanomas in situ are going to be missed if PAs perform unsupervised skin cancer screenings. This is not a tenable proposition, ethically or legally. Dermatologists and PAs need to work together to ensure this does not happen.

An estimated 2,520 dermatology PAs were practicing in the United States in 2016, based on membership data from the Society of Dermatology PAs (SDPA), according to a research letter published last year (J Am Acad Dermatol. 2017 Jun;76[6]:1200-2). The SDPA, as stated in an SDPA position statement published in the winter 2017 newsletter, hopes to gain access to direct billing to public and private insurers, which would include the Centers for Medicare & Medicaid Services, and for PAs to no longer report to other health care professionals.

 

Many dermatologists, as well as teaching programs, use PAs to perform skin cancer screenings, sometimes unsupervised, which makes diagnostic accuracy critical. The issues at hand are the safety of patients and the accuracy of diagnosis as well as the costs to the health care system. A team effort, which includes direct supervision, is needed to ensure those issues are addressed.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

 

The emergency department locum tenens staff recruiter was persuasive. “It’s a quiet little ER where you can study and sleep.” I was board certified in internal medicine and had trained in a busy urban emergency department. This was just the spot to make a little folding money and study for my mock dermatology boards, I thought.

And so, on a Saturday night in rural Texas, after grinding rust out of a pipe fitter’s eye and stitching up two brawlers from the local biker bar, I was faced with treating a comatose kid brought in after a car crash. He had not been wearing a seat belt, and his car had rolled over on his head.

I was way over my skill level, but I was lucky. I was able to stabilize him and, after several long hours, I got him on an emergency helicopter into Dallas.

But the experience changed me. I realized I did not know enough to deal with this case on my own. After making it through that night in the ED, I never put myself in that position again.

I now knew what I did not know.

A study recently published in JAMA Dermatology reminded me of that experience in Texas. The study compared the accuracy of skin cancer diagnoses by physician assistants (PAs) and dermatologists for about 20,000 patients and 33,000 patient encounters for skin cancer screening between January 2011 and December 2015 at dermatology offices affiliated with the University of Pittsburgh. No significant differences in diagnoses of nonmelanoma skin cancer and invasive melanoma were found.

The finding that jumped out to me, though, was that patients screened by a PA were significantly less likely to be diagnosed with melanoma in situ, the stage when melanoma is 100% curable. Yet, those patients screened by PAs underwent a lot more skin biopsies – 36% more skin biopsies per melanoma in situ diagnosed, compared with patients of dermatologists. Interestingly, in the health care system studied, any PA with a question about a patient can ask an attending dermatologist to see the patient. Did that factor account for the diagnostic comparability for nonmelanoma skin cancer and invasive melanoma? Did the PAs not ask for help on the missed melanomas in situ? If so, I believe this may be a situation of PAs not knowing what they didn’t know.

 

Now a knowledgeable friend of mine thinks this study is biased because 17% more patients with prior melanomas were seen by a dermatologist rather than by a PA. While it’s true that patients with prior melanomas are more likely to develop new melanomas, the counterargument is that the bar for a biopsy in a patient with a prior melanoma is much lower. Patients with a history of melanoma should have more skin biopsies, but the dermatologists in this study still took many fewer biopsies to diagnose melanomas in situ.

Why do these findings matter for patients and for the health care system?

PAs billed independently for 12% of skin biopsies (including lip, ear, ear canal, vulva, penis, and eyelid) in Medicare Fee for Service in 2016. Skin biopsies paid for by Medicare have been increasing at a very rapid rate, about twice as fast as the rate reflected in the current skin cancer epidemic.

Every skin biopsy results in a pathology charge, for which Medicare pays about $70. A level 3 new patient visit pays $110. If PAs bill independently, they are paid at 85% of the fee schedule, which often is touted as a great savings. Therefore, if only 24.2% of skin biopsies by PAs were unnecessary, even at a reduced 85% reimbursement, it costs Medicare more than having these visits and biopsies provided by a dermatologist. The cost savings decrease even more with additional skin biopsies, because they pay so little ($33 for a doctor, $28 for a PA), yet the pathology charge is unchanged.

 

There are other costs beyond monetary ones from unnecessary skin biopsies: scarring, follow-up procedures for uncertain diagnoses such as mild dysplastic nevi, ambiguous results, and emotional angst to patients.

Further, three new skin biopsy CPT codes have recently been surveyed by the Relative Value Scale Update Committee, which means that the increasing number of skin biopsies has triggered a review. This is not good news.Dermatology appears simple and easy, but in fact it is not. While less dramatic than a closed head injury, a missed melanoma in situ can be just as deadly. It is hard to know when you do not know something.

If the results of this large study are to be believed, many melanomas in situ are going to be missed if PAs perform unsupervised skin cancer screenings. This is not a tenable proposition, ethically or legally. Dermatologists and PAs need to work together to ensure this does not happen.

An estimated 2,520 dermatology PAs were practicing in the United States in 2016, based on membership data from the Society of Dermatology PAs (SDPA), according to a research letter published last year (J Am Acad Dermatol. 2017 Jun;76[6]:1200-2). The SDPA, as stated in an SDPA position statement published in the winter 2017 newsletter, hopes to gain access to direct billing to public and private insurers, which would include the Centers for Medicare & Medicaid Services, and for PAs to no longer report to other health care professionals.

 

Many dermatologists, as well as teaching programs, use PAs to perform skin cancer screenings, sometimes unsupervised, which makes diagnostic accuracy critical. The issues at hand are the safety of patients and the accuracy of diagnosis as well as the costs to the health care system. A team effort, which includes direct supervision, is needed to ensure those issues are addressed.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

 

One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.¹

Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.

Two major clinical trials, the SOFT and TEXT trials, explored the benefit of ovarian ablation in the adjuvant treatment of early stage premenopausal breast cancer. The SOFT trial included 3,066 women randomized to receive tamoxifen, tamoxifen with ovarian suppression, or an aromatase inhibitor with ovarian suppression.² In the TEXT trial, 2,672 patients were randomized to receive either an aromatase inhibitor with ovarian suppression or tamoxifen with ovarian suppression.³ Results of the two trials showed that there was greatest treatment effect when ovarian suppression is added to tamoxifen, or in patients receiving an aromatase inhibitor with ovarian suppression. This effect appeared to be dominant among women who had received prior chemotherapy and were at higher risk for recurrence, and who remained premenopausal after completion of their primary therapy. While ovarian suppression was associated with improved disease-free survival, it was not associated with an increased overall survival.

In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.⁴ It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.

BRCA populations

For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.⁵

Technique

When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.

The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.

 

The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.⁶ Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.

Consequences of ovarian ablation

It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.^7,8

It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.

Hormone replacement therapy postoperatively

Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.

 

Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.

2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.

3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.

4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.

5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.

6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.

7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.

8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.

 

One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.¹

Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.

Two major clinical trials, the SOFT and TEXT trials, explored the benefit of ovarian ablation in the adjuvant treatment of early stage premenopausal breast cancer. The SOFT trial included 3,066 women randomized to receive tamoxifen, tamoxifen with ovarian suppression, or an aromatase inhibitor with ovarian suppression.² In the TEXT trial, 2,672 patients were randomized to receive either an aromatase inhibitor with ovarian suppression or tamoxifen with ovarian suppression.³ Results of the two trials showed that there was greatest treatment effect when ovarian suppression is added to tamoxifen, or in patients receiving an aromatase inhibitor with ovarian suppression. This effect appeared to be dominant among women who had received prior chemotherapy and were at higher risk for recurrence, and who remained premenopausal after completion of their primary therapy. While ovarian suppression was associated with improved disease-free survival, it was not associated with an increased overall survival.

In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.⁴ It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.

BRCA populations

For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.⁵

Technique

When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.

The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.

 

The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.⁶ Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.

Consequences of ovarian ablation

It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.^7,8

It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.

Hormone replacement therapy postoperatively

Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.

 

Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.

2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.

3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.

4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.

5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.

6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.

7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.

8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.

 

One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.¹

Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.

Two major clinical trials, the SOFT and TEXT trials, explored the benefit of ovarian ablation in the adjuvant treatment of early stage premenopausal breast cancer. The SOFT trial included 3,066 women randomized to receive tamoxifen, tamoxifen with ovarian suppression, or an aromatase inhibitor with ovarian suppression.² In the TEXT trial, 2,672 patients were randomized to receive either an aromatase inhibitor with ovarian suppression or tamoxifen with ovarian suppression.³ Results of the two trials showed that there was greatest treatment effect when ovarian suppression is added to tamoxifen, or in patients receiving an aromatase inhibitor with ovarian suppression. This effect appeared to be dominant among women who had received prior chemotherapy and were at higher risk for recurrence, and who remained premenopausal after completion of their primary therapy. While ovarian suppression was associated with improved disease-free survival, it was not associated with an increased overall survival.

In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.⁴ It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.

BRCA populations

For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.⁵

Technique

When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.

The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.

 

The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.⁶ Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.

Consequences of ovarian ablation

It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.^7,8

It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.

Hormone replacement therapy postoperatively

Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.

 

Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.

2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.

3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.

4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.

5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.

6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.

7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.

8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.

 

Collagen drinks and supplements have been getting a lot of buzz lately, from media advertisements and patients asking us about them. The question is, do they really do anything? Previously, most collagen supplements in the beauty industry came in the form of a topical cream or an injectable, with collagen being the main filler of choice before hyaluronic acid fillers became available. Today, collagen supplementation in the form of oral pills and drinks is rampant. These drinks and “vitamins” are purported to improve skin and provide a more youthful appearance, both from an immediate and preventative standpoint. Some of the drinks come from companies in Japan and beyond. According to market forecasts, the collagen supplement industry is anticipated to be worth $6.63 billion by 2025, up from $3.71 billion in 2016. An email advertisement this month from NewBeauty magazine claims one brand of collagen supplementation “with grape seed extract [as] an effective collagen drink for the skin.” Each 1.7 oz. bottle contains 13,000 mg of marine hydrolyzed collagen with six antiaging ingredients that – the ad claims – will help visibly transform your skin to a fuller, firmer, younger look in as soon as 21 days.

Diet absolutely plays a role in our overall health and skin appearance. But can these concentrated collagen drinks provide an increased benefit?

marekuliasz/iStock/Getty Images Plus

Hydrolyzed collagen is often derived from bovine bone and cartilage. Usually, the bone is crushed, ground, defatted, soaked in acid to remove the calcium, soaked again to break the collagen bonds, and then dehydrated, and typically ends up in the form of a powder. In this form, it is soluble in cold liquids and easily digestible. Hydrolyzed collagen taken orally has been shown to have antioxidant properties, antihypertensive and lipid-lowering activity, as well as reparative properties in damaged skin. Besides this, oral collagen supplementation has not been studied, and research in peer-reviewed journals has not yet been published demonstrating it’s benefit for skin and beauty (J Cosmet Dermatol. 2018 Feb;17[1]:20-6).

We know from prior experience with injecting collagen in the lips – namely from bovine (such as Zyderm and Zyplast) or human-derived (such as Cosmoderm and CosmoPlast) sources – that it provided beautiful and often natural-appearing results, which, however, did not last. If longevity is an issue with collagen injections, assuming proper absorption from the gastrointestinal tract and subsequent integration into skin, how long should we expect the results from drinking collagen to last in skin, if any? If it does work and is something that improves skin when used on a continuous basis, is there an endpoint at which the benefit is maximized or where an excess of collagen could be detrimental?

Collagen disorders are those where there is inflammation or deficiency in collagen. Could supplementation improve these diseases? Or could supplementation exacerbate or bring on these disorders if consumed in excess? In collagen vascular diseases, such as scleroderma, where apparent autoimmune inflammation of collagen occurs, would supplementation exacerbate the disease by bringing about more collagen to attack, or would it improve the condition by providing new collagen where there may be a defect? Would it help in conditions of collagen deficiency, such as osteogenesis imperfecta?

The source and type of collagen may also provide a difference in the effect it has, if any. Collagen itself has to come from an animal, a human, or a synthetic source. Animal sources are most commonly from bovine and porcine sources, although marine sources are increasingly being used. Bovine was once the most commonly used (as with Zyderm and Zyplast). Bovine collagen presents the risk of allergenicity and, less commonly, bovine spongiform encephalopathy. Plants do not contain collagen, but are purported to help boost ones own natural collagen by providing a source of vitamins and nutrients required for collagen production/remodeling. For example, carrots and sweet potatoes are rich in vitamin A, and vitamin A derivatives such as isotretinoin and tretinoin have been shown to provide collagen remodeling in improving acne, skin texture, and wrinkles. In a clinical trial, an oral drink containing soy, antioxidants (soy isoflavones, lycopene, Vitamins C and E), and a capsule of fish oil was shown to reduce facial-wrinkle depth in postmenopausal women thought to be caused by new collagen deposition (Int J Cosmet Sci. 2014 Feb;36[1]:22-31).

Type I collagen is found in tendon, ligaments, bone, and cornea. Types I, III, IV, and VII are the most predominate in skin (I in scar tissue, III in normal dermis, IV in basement membrane, and VII in dermal-epidermal junctions). With at least 28 types of collagen in the human body, perhaps the type of collagen being supplemented might play a role in where it is integrated and whether it benefits skin versus other tissues.

 

Many questions about collagen drinks and supplementation remain to be answered. Photoprotection from an early age and a healthy diet that supports production of our bodies’ own natural collagen are the best measures for skin health. With the surplus of collagen drinks and supplements now on the market, objective studies should be conducted and are warranted to answer these question for ourselves and our patients.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

 

Collagen drinks and supplements have been getting a lot of buzz lately, from media advertisements and patients asking us about them. The question is, do they really do anything? Previously, most collagen supplements in the beauty industry came in the form of a topical cream or an injectable, with collagen being the main filler of choice before hyaluronic acid fillers became available. Today, collagen supplementation in the form of oral pills and drinks is rampant. These drinks and “vitamins” are purported to improve skin and provide a more youthful appearance, both from an immediate and preventative standpoint. Some of the drinks come from companies in Japan and beyond. According to market forecasts, the collagen supplement industry is anticipated to be worth $6.63 billion by 2025, up from $3.71 billion in 2016. An email advertisement this month from NewBeauty magazine claims one brand of collagen supplementation “with grape seed extract [as] an effective collagen drink for the skin.” Each 1.7 oz. bottle contains 13,000 mg of marine hydrolyzed collagen with six antiaging ingredients that – the ad claims – will help visibly transform your skin to a fuller, firmer, younger look in as soon as 21 days.

Diet absolutely plays a role in our overall health and skin appearance. But can these concentrated collagen drinks provide an increased benefit?

marekuliasz/iStock/Getty Images Plus

Hydrolyzed collagen is often derived from bovine bone and cartilage. Usually, the bone is crushed, ground, defatted, soaked in acid to remove the calcium, soaked again to break the collagen bonds, and then dehydrated, and typically ends up in the form of a powder. In this form, it is soluble in cold liquids and easily digestible. Hydrolyzed collagen taken orally has been shown to have antioxidant properties, antihypertensive and lipid-lowering activity, as well as reparative properties in damaged skin. Besides this, oral collagen supplementation has not been studied, and research in peer-reviewed journals has not yet been published demonstrating it’s benefit for skin and beauty (J Cosmet Dermatol. 2018 Feb;17[1]:20-6).

We know from prior experience with injecting collagen in the lips – namely from bovine (such as Zyderm and Zyplast) or human-derived (such as Cosmoderm and CosmoPlast) sources – that it provided beautiful and often natural-appearing results, which, however, did not last. If longevity is an issue with collagen injections, assuming proper absorption from the gastrointestinal tract and subsequent integration into skin, how long should we expect the results from drinking collagen to last in skin, if any? If it does work and is something that improves skin when used on a continuous basis, is there an endpoint at which the benefit is maximized or where an excess of collagen could be detrimental?

Collagen disorders are those where there is inflammation or deficiency in collagen. Could supplementation improve these diseases? Or could supplementation exacerbate or bring on these disorders if consumed in excess? In collagen vascular diseases, such as scleroderma, where apparent autoimmune inflammation of collagen occurs, would supplementation exacerbate the disease by bringing about more collagen to attack, or would it improve the condition by providing new collagen where there may be a defect? Would it help in conditions of collagen deficiency, such as osteogenesis imperfecta?

The source and type of collagen may also provide a difference in the effect it has, if any. Collagen itself has to come from an animal, a human, or a synthetic source. Animal sources are most commonly from bovine and porcine sources, although marine sources are increasingly being used. Bovine was once the most commonly used (as with Zyderm and Zyplast). Bovine collagen presents the risk of allergenicity and, less commonly, bovine spongiform encephalopathy. Plants do not contain collagen, but are purported to help boost ones own natural collagen by providing a source of vitamins and nutrients required for collagen production/remodeling. For example, carrots and sweet potatoes are rich in vitamin A, and vitamin A derivatives such as isotretinoin and tretinoin have been shown to provide collagen remodeling in improving acne, skin texture, and wrinkles. In a clinical trial, an oral drink containing soy, antioxidants (soy isoflavones, lycopene, Vitamins C and E), and a capsule of fish oil was shown to reduce facial-wrinkle depth in postmenopausal women thought to be caused by new collagen deposition (Int J Cosmet Sci. 2014 Feb;36[1]:22-31).

Type I collagen is found in tendon, ligaments, bone, and cornea. Types I, III, IV, and VII are the most predominate in skin (I in scar tissue, III in normal dermis, IV in basement membrane, and VII in dermal-epidermal junctions). With at least 28 types of collagen in the human body, perhaps the type of collagen being supplemented might play a role in where it is integrated and whether it benefits skin versus other tissues.

 

Many questions about collagen drinks and supplementation remain to be answered. Photoprotection from an early age and a healthy diet that supports production of our bodies’ own natural collagen are the best measures for skin health. With the surplus of collagen drinks and supplements now on the market, objective studies should be conducted and are warranted to answer these question for ourselves and our patients.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

 

Collagen drinks and supplements have been getting a lot of buzz lately, from media advertisements and patients asking us about them. The question is, do they really do anything? Previously, most collagen supplements in the beauty industry came in the form of a topical cream or an injectable, with collagen being the main filler of choice before hyaluronic acid fillers became available. Today, collagen supplementation in the form of oral pills and drinks is rampant. These drinks and “vitamins” are purported to improve skin and provide a more youthful appearance, both from an immediate and preventative standpoint. Some of the drinks come from companies in Japan and beyond. According to market forecasts, the collagen supplement industry is anticipated to be worth $6.63 billion by 2025, up from $3.71 billion in 2016. An email advertisement this month from NewBeauty magazine claims one brand of collagen supplementation “with grape seed extract [as] an effective collagen drink for the skin.” Each 1.7 oz. bottle contains 13,000 mg of marine hydrolyzed collagen with six antiaging ingredients that – the ad claims – will help visibly transform your skin to a fuller, firmer, younger look in as soon as 21 days.

Diet absolutely plays a role in our overall health and skin appearance. But can these concentrated collagen drinks provide an increased benefit?

marekuliasz/iStock/Getty Images Plus

Hydrolyzed collagen is often derived from bovine bone and cartilage. Usually, the bone is crushed, ground, defatted, soaked in acid to remove the calcium, soaked again to break the collagen bonds, and then dehydrated, and typically ends up in the form of a powder. In this form, it is soluble in cold liquids and easily digestible. Hydrolyzed collagen taken orally has been shown to have antioxidant properties, antihypertensive and lipid-lowering activity, as well as reparative properties in damaged skin. Besides this, oral collagen supplementation has not been studied, and research in peer-reviewed journals has not yet been published demonstrating it’s benefit for skin and beauty (J Cosmet Dermatol. 2018 Feb;17[1]:20-6).

We know from prior experience with injecting collagen in the lips – namely from bovine (such as Zyderm and Zyplast) or human-derived (such as Cosmoderm and CosmoPlast) sources – that it provided beautiful and often natural-appearing results, which, however, did not last. If longevity is an issue with collagen injections, assuming proper absorption from the gastrointestinal tract and subsequent integration into skin, how long should we expect the results from drinking collagen to last in skin, if any? If it does work and is something that improves skin when used on a continuous basis, is there an endpoint at which the benefit is maximized or where an excess of collagen could be detrimental?

Collagen disorders are those where there is inflammation or deficiency in collagen. Could supplementation improve these diseases? Or could supplementation exacerbate or bring on these disorders if consumed in excess? In collagen vascular diseases, such as scleroderma, where apparent autoimmune inflammation of collagen occurs, would supplementation exacerbate the disease by bringing about more collagen to attack, or would it improve the condition by providing new collagen where there may be a defect? Would it help in conditions of collagen deficiency, such as osteogenesis imperfecta?

The source and type of collagen may also provide a difference in the effect it has, if any. Collagen itself has to come from an animal, a human, or a synthetic source. Animal sources are most commonly from bovine and porcine sources, although marine sources are increasingly being used. Bovine was once the most commonly used (as with Zyderm and Zyplast). Bovine collagen presents the risk of allergenicity and, less commonly, bovine spongiform encephalopathy. Plants do not contain collagen, but are purported to help boost ones own natural collagen by providing a source of vitamins and nutrients required for collagen production/remodeling. For example, carrots and sweet potatoes are rich in vitamin A, and vitamin A derivatives such as isotretinoin and tretinoin have been shown to provide collagen remodeling in improving acne, skin texture, and wrinkles. In a clinical trial, an oral drink containing soy, antioxidants (soy isoflavones, lycopene, Vitamins C and E), and a capsule of fish oil was shown to reduce facial-wrinkle depth in postmenopausal women thought to be caused by new collagen deposition (Int J Cosmet Sci. 2014 Feb;36[1]:22-31).

Type I collagen is found in tendon, ligaments, bone, and cornea. Types I, III, IV, and VII are the most predominate in skin (I in scar tissue, III in normal dermis, IV in basement membrane, and VII in dermal-epidermal junctions). With at least 28 types of collagen in the human body, perhaps the type of collagen being supplemented might play a role in where it is integrated and whether it benefits skin versus other tissues.

 

Many questions about collagen drinks and supplementation remain to be answered. Photoprotection from an early age and a healthy diet that supports production of our bodies’ own natural collagen are the best measures for skin health. With the surplus of collagen drinks and supplements now on the market, objective studies should be conducted and are warranted to answer these question for ourselves and our patients.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

 

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Physicians continually are reminded that we should use antibiotics only when we have determined that they are warranted to treat a specific condition. Prophylaxis is frowned upon and a practice to be applied only when there is a demonstrated benefit of significant magnitude. To do otherwise opens a Pandora’s box, thereby releasing a flock of miseries and unintended consequences, foremost of which is the emergence of resistant strains of bacteria that can threaten the population we are committed to protecting.

Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.

When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.

Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.

Giving prophylactic antibiotics to an entire population is clearly a double-edged sword. How does one develop criteria for choosing which populations will benefit enough to put its members and its neighbors at risk for antibiotic resistance? That the children of Niger benefited most suggests there might be some threshold effect that could be determined. Who should be making the decision about which populations to treat? Money wasn’t a problem in this study thanks to the Bill and Melinda Gates Foundation.

And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Physicians continually are reminded that we should use antibiotics only when we have determined that they are warranted to treat a specific condition. Prophylaxis is frowned upon and a practice to be applied only when there is a demonstrated benefit of significant magnitude. To do otherwise opens a Pandora’s box, thereby releasing a flock of miseries and unintended consequences, foremost of which is the emergence of resistant strains of bacteria that can threaten the population we are committed to protecting.

Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.

When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.

Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.

Giving prophylactic antibiotics to an entire population is clearly a double-edged sword. How does one develop criteria for choosing which populations will benefit enough to put its members and its neighbors at risk for antibiotic resistance? That the children of Niger benefited most suggests there might be some threshold effect that could be determined. Who should be making the decision about which populations to treat? Money wasn’t a problem in this study thanks to the Bill and Melinda Gates Foundation.

And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Physicians continually are reminded that we should use antibiotics only when we have determined that they are warranted to treat a specific condition. Prophylaxis is frowned upon and a practice to be applied only when there is a demonstrated benefit of significant magnitude. To do otherwise opens a Pandora’s box, thereby releasing a flock of miseries and unintended consequences, foremost of which is the emergence of resistant strains of bacteria that can threaten the population we are committed to protecting.

Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.

When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.

Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.

Giving prophylactic antibiotics to an entire population is clearly a double-edged sword. How does one develop criteria for choosing which populations will benefit enough to put its members and its neighbors at risk for antibiotic resistance? That the children of Niger benefited most suggests there might be some threshold effect that could be determined. Who should be making the decision about which populations to treat? Money wasn’t a problem in this study thanks to the Bill and Melinda Gates Foundation.

And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?

If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.

If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.

On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.

You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.

DenGuy/iStock/Getty Images

Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.

The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?

If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.

If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.

On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.

You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.

DenGuy/iStock/Getty Images

Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.

The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?

If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.

If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.

On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.

You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.

DenGuy/iStock/Getty Images

Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.

The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

 

Darrin Klimek/Thinkstock

Like everyone in the arc of social media impact, I was shocked and terribly saddened by the recent suicides of two New York women in medicine – a final-year medical student on May 1 and a second-year resident on May 5. As a specialist in physician health, a former training director, a long-standing member of our institution’s medical student admissions committee, and the ombudsman for our medical students, I am finding these tragedies harder and harder to reconcile. Something isn’t working. But before I get to that, what follows is a bulleted list of some events of the past couple of weeks that may give a context for my statements and have informed my two recommendations.

• May 3, 2018: I give an invited GI grand rounds on stress, burnout, depression, and suicide in physicians. The residents are quiet and say nothing. Faculty members seem only concerned about preventing and eradicating burnout – and not that interested in anything more severe.
• May 5: A psychiatry resident from Melbourne arrives to spend 10 days with me to do an elective in physician health. As in the United States, there is a significant suicide death rate in medical students and residents Down Under. In the afternoon, I present a paper at the annual meeting of the American Academy of Psychodynamic Psychiatry and Psychoanalysis on the use of psychotherapy in treatment-resistant suicidal depression in physicians. There is increasing hope that this essential modality of care will return to the contemporary psychiatrist’s toolbox.
• May 6: At the annual meeting of the American Psychiatric Association in New York, I’m the discussant for powerful heartfelt papers of five psychiatrists (mostly early career psychiatrists and one resident) that talked about living with a psychiatric illness. The audience is huge, and we hear narratives about internal stigma, self-disclosure, external stigma, shunning, bullying, acceptance, rejection, alienation, connection, and love by peers and family. The authenticity and valor of the speakers create an atmosphere of safety, which enables psychiatrists in attendance from all over the world to share their personal stories – some at the microphone, some privately.
• May 7: Again at the APA, I chair and facilitate a workshop on physician suicide. We hear from four speakers, all women, who have lost a loved one to suicide – a husband, a father, a brother, a son – all doctors. Two of the speakers are psychiatrists. The stories are gripping, detailed, and tender. Yes, the atmosphere is very sad, but there is not a pall. We learn how these doctors lived, not just how they died. They all loved medicine; they were creative; they cared deeply; they suffered silently; and with shame, they lost hope. Again, a big audience of psychiatrists, many of whom share their own stories, that they, too, had lost a physician son, wife, or mother to suicide. Some of their deceased family members fell through the cracks and did not receive the life-saving care they deserved; some, fearing assaults to their medical license, hospital privileges, or insurance, refused to see anyone. They died untreated.
• May 8: Still at the APA, a psychiatrist colleague and I collaborate on a clinical case conference. Each of us describes losing a physician patient to suicide. We walk the attendees through the clinical details of assessment, treatment, and the aftermath of their deaths. We talk openly and frankly about our feelings, grief, outreach to colleagues and the family, and our own personal journeys of learning, growth, and healing. The clinician audience members give constructive feedback, and some share their own stories of losing patients to suicide. Like the day before, some psychiatrists are grieving the loss of a physician son or sibling to suicide. As mental health professionals, they suffer from an additional layer of failure and guilt that a loved one died “under their watch.”
• May 8: I rush across the Javits Center to catch the discussant for a concurrent symposium on physician burnout and depression. She foregoes any prepared remarks to share her previous 48 hours with the audience. She is the training director of the program that lost the second-year resident on May 5. She did not learn of the death until 24 hours later. We are all on the edge of our seats as we listen to this grieving, courageous woman, a seasoned psychiatrist and educator, who has been blindsided by this tragedy. She has not slept. She called all of her residents and broke the news personally as best she could. Aided by “After A Suicide: A Toolkit for Residency/Fellowship Programs” (American Foundation for Suicide Prevention), she and her colleagues instituted a plan of action and worked with administration and faculty. Her strength and commitment to the well-being of her trainees is palpable and magnanimous. When the session ends, many of us stand in line to give her a hug. It is a stark reminder of how many lives are affected when someone you know or care about takes his/her own life – and how, in the house of medicine, medical students and residents really are part of an institutional family.
• May 10: I facilitate a meeting of our 12 second-year residents, many of whom knew of or had met the resident who died. Almost everyone speaks, shares their feelings, poses questions, and calls for answers and change. There is disbelief, sadness, confusion, some guilt, and lots of anger. Also a feeling of disillusionment or paradox about the field of psychiatry: “Of all branches of medicine, shouldn’t residents who are struggling with psychiatric issues feel safe, protected, cared for in psychiatry?” There is also a feeling of lip service being paid to personal treatment, as in quoted statements: “By all means, get treatment for your issues, but don’t let it encroach on your duty hours” or “It’s good you’re getting help, but do you still have to go weekly?”

 

In the immediate aftermath of suicide, feelings run high, as they should. But rather than wait it out – and fearing a return to “business as usual” – let me make only two suggestions:

1. We need to come together and talk about this – medical students and residents and training directors and deans. A town hall forum would be ideal. Although there are amazing innovations on wellness emanating from the Association of American Medical Colleges and Accreditation Council for Graduate Medical Education, many current medical students and residents feel frustrated – “This is taking too long” or “This is top down and being imposed on us” or “What about our voices … don’t they count?” Although students and residents have representatives on faculty committees, feedback is not universal, and not all residents believe that their senior peers truly convey their concerns to those in power. They want to be present at the table and speak for themselves. Too many do not feel they have a voice.

2. In psychiatry, we need to redouble our efforts in fighting the stigma attached to psychiatric illness in trainees. It is unconscionable that medical students and residents are dying of treatable disorders (I’ve never heard of a doctor dying of cancer who didn’t go to an oncologist at least once), yet too many are not availing themselves of services we provide – even when they’re free of charge or covered by insurance. And are we certain that, when they knock on our doors, we are providing them with state-of-the-art care? Is it possible that unrecognized internal stigma and shame deep within us might make us hesitant to help our trainees in their hour of need? Or cut corners? Or not get a second opinion? Very few psychiatrists on faculty of our medical schools divulge their personal experiences of depression, posttraumatic stress disorders, substance use disorders, and more (with the exception of being in therapy during residency, which is normative and isn’t stigmatized). Coming out is leveling, humane, and respectful – and it shrinks the power differential in the teaching dyad. It might even save a life.
 

Dr. Myers is a professor of clinical psychiatry at State University of New York, Brooklyn, and the author of “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared.”
 

 

Darrin Klimek/Thinkstock

Like everyone in the arc of social media impact, I was shocked and terribly saddened by the recent suicides of two New York women in medicine – a final-year medical student on May 1 and a second-year resident on May 5. As a specialist in physician health, a former training director, a long-standing member of our institution’s medical student admissions committee, and the ombudsman for our medical students, I am finding these tragedies harder and harder to reconcile. Something isn’t working. But before I get to that, what follows is a bulleted list of some events of the past couple of weeks that may give a context for my statements and have informed my two recommendations.

• May 3, 2018: I give an invited GI grand rounds on stress, burnout, depression, and suicide in physicians. The residents are quiet and say nothing. Faculty members seem only concerned about preventing and eradicating burnout – and not that interested in anything more severe.
• May 5: A psychiatry resident from Melbourne arrives to spend 10 days with me to do an elective in physician health. As in the United States, there is a significant suicide death rate in medical students and residents Down Under. In the afternoon, I present a paper at the annual meeting of the American Academy of Psychodynamic Psychiatry and Psychoanalysis on the use of psychotherapy in treatment-resistant suicidal depression in physicians. There is increasing hope that this essential modality of care will return to the contemporary psychiatrist’s toolbox.
• May 6: At the annual meeting of the American Psychiatric Association in New York, I’m the discussant for powerful heartfelt papers of five psychiatrists (mostly early career psychiatrists and one resident) that talked about living with a psychiatric illness. The audience is huge, and we hear narratives about internal stigma, self-disclosure, external stigma, shunning, bullying, acceptance, rejection, alienation, connection, and love by peers and family. The authenticity and valor of the speakers create an atmosphere of safety, which enables psychiatrists in attendance from all over the world to share their personal stories – some at the microphone, some privately.
• May 7: Again at the APA, I chair and facilitate a workshop on physician suicide. We hear from four speakers, all women, who have lost a loved one to suicide – a husband, a father, a brother, a son – all doctors. Two of the speakers are psychiatrists. The stories are gripping, detailed, and tender. Yes, the atmosphere is very sad, but there is not a pall. We learn how these doctors lived, not just how they died. They all loved medicine; they were creative; they cared deeply; they suffered silently; and with shame, they lost hope. Again, a big audience of psychiatrists, many of whom share their own stories, that they, too, had lost a physician son, wife, or mother to suicide. Some of their deceased family members fell through the cracks and did not receive the life-saving care they deserved; some, fearing assaults to their medical license, hospital privileges, or insurance, refused to see anyone. They died untreated.
• May 8: Still at the APA, a psychiatrist colleague and I collaborate on a clinical case conference. Each of us describes losing a physician patient to suicide. We walk the attendees through the clinical details of assessment, treatment, and the aftermath of their deaths. We talk openly and frankly about our feelings, grief, outreach to colleagues and the family, and our own personal journeys of learning, growth, and healing. The clinician audience members give constructive feedback, and some share their own stories of losing patients to suicide. Like the day before, some psychiatrists are grieving the loss of a physician son or sibling to suicide. As mental health professionals, they suffer from an additional layer of failure and guilt that a loved one died “under their watch.”
• May 8: I rush across the Javits Center to catch the discussant for a concurrent symposium on physician burnout and depression. She foregoes any prepared remarks to share her previous 48 hours with the audience. She is the training director of the program that lost the second-year resident on May 5. She did not learn of the death until 24 hours later. We are all on the edge of our seats as we listen to this grieving, courageous woman, a seasoned psychiatrist and educator, who has been blindsided by this tragedy. She has not slept. She called all of her residents and broke the news personally as best she could. Aided by “After A Suicide: A Toolkit for Residency/Fellowship Programs” (American Foundation for Suicide Prevention), she and her colleagues instituted a plan of action and worked with administration and faculty. Her strength and commitment to the well-being of her trainees is palpable and magnanimous. When the session ends, many of us stand in line to give her a hug. It is a stark reminder of how many lives are affected when someone you know or care about takes his/her own life – and how, in the house of medicine, medical students and residents really are part of an institutional family.
• May 10: I facilitate a meeting of our 12 second-year residents, many of whom knew of or had met the resident who died. Almost everyone speaks, shares their feelings, poses questions, and calls for answers and change. There is disbelief, sadness, confusion, some guilt, and lots of anger. Also a feeling of disillusionment or paradox about the field of psychiatry: “Of all branches of medicine, shouldn’t residents who are struggling with psychiatric issues feel safe, protected, cared for in psychiatry?” There is also a feeling of lip service being paid to personal treatment, as in quoted statements: “By all means, get treatment for your issues, but don’t let it encroach on your duty hours” or “It’s good you’re getting help, but do you still have to go weekly?”

 

In the immediate aftermath of suicide, feelings run high, as they should. But rather than wait it out – and fearing a return to “business as usual” – let me make only two suggestions:

1. We need to come together and talk about this – medical students and residents and training directors and deans. A town hall forum would be ideal. Although there are amazing innovations on wellness emanating from the Association of American Medical Colleges and Accreditation Council for Graduate Medical Education, many current medical students and residents feel frustrated – “This is taking too long” or “This is top down and being imposed on us” or “What about our voices … don’t they count?” Although students and residents have representatives on faculty committees, feedback is not universal, and not all residents believe that their senior peers truly convey their concerns to those in power. They want to be present at the table and speak for themselves. Too many do not feel they have a voice.

2. In psychiatry, we need to redouble our efforts in fighting the stigma attached to psychiatric illness in trainees. It is unconscionable that medical students and residents are dying of treatable disorders (I’ve never heard of a doctor dying of cancer who didn’t go to an oncologist at least once), yet too many are not availing themselves of services we provide – even when they’re free of charge or covered by insurance. And are we certain that, when they knock on our doors, we are providing them with state-of-the-art care? Is it possible that unrecognized internal stigma and shame deep within us might make us hesitant to help our trainees in their hour of need? Or cut corners? Or not get a second opinion? Very few psychiatrists on faculty of our medical schools divulge their personal experiences of depression, posttraumatic stress disorders, substance use disorders, and more (with the exception of being in therapy during residency, which is normative and isn’t stigmatized). Coming out is leveling, humane, and respectful – and it shrinks the power differential in the teaching dyad. It might even save a life.
 

Dr. Myers is a professor of clinical psychiatry at State University of New York, Brooklyn, and the author of “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared.”
 

 

Darrin Klimek/Thinkstock

Like everyone in the arc of social media impact, I was shocked and terribly saddened by the recent suicides of two New York women in medicine – a final-year medical student on May 1 and a second-year resident on May 5. As a specialist in physician health, a former training director, a long-standing member of our institution’s medical student admissions committee, and the ombudsman for our medical students, I am finding these tragedies harder and harder to reconcile. Something isn’t working. But before I get to that, what follows is a bulleted list of some events of the past couple of weeks that may give a context for my statements and have informed my two recommendations.

• May 3, 2018: I give an invited GI grand rounds on stress, burnout, depression, and suicide in physicians. The residents are quiet and say nothing. Faculty members seem only concerned about preventing and eradicating burnout – and not that interested in anything more severe.
• May 5: A psychiatry resident from Melbourne arrives to spend 10 days with me to do an elective in physician health. As in the United States, there is a significant suicide death rate in medical students and residents Down Under. In the afternoon, I present a paper at the annual meeting of the American Academy of Psychodynamic Psychiatry and Psychoanalysis on the use of psychotherapy in treatment-resistant suicidal depression in physicians. There is increasing hope that this essential modality of care will return to the contemporary psychiatrist’s toolbox.
• May 6: At the annual meeting of the American Psychiatric Association in New York, I’m the discussant for powerful heartfelt papers of five psychiatrists (mostly early career psychiatrists and one resident) that talked about living with a psychiatric illness. The audience is huge, and we hear narratives about internal stigma, self-disclosure, external stigma, shunning, bullying, acceptance, rejection, alienation, connection, and love by peers and family. The authenticity and valor of the speakers create an atmosphere of safety, which enables psychiatrists in attendance from all over the world to share their personal stories – some at the microphone, some privately.
• May 7: Again at the APA, I chair and facilitate a workshop on physician suicide. We hear from four speakers, all women, who have lost a loved one to suicide – a husband, a father, a brother, a son – all doctors. Two of the speakers are psychiatrists. The stories are gripping, detailed, and tender. Yes, the atmosphere is very sad, but there is not a pall. We learn how these doctors lived, not just how they died. They all loved medicine; they were creative; they cared deeply; they suffered silently; and with shame, they lost hope. Again, a big audience of psychiatrists, many of whom share their own stories, that they, too, had lost a physician son, wife, or mother to suicide. Some of their deceased family members fell through the cracks and did not receive the life-saving care they deserved; some, fearing assaults to their medical license, hospital privileges, or insurance, refused to see anyone. They died untreated.
• May 8: Still at the APA, a psychiatrist colleague and I collaborate on a clinical case conference. Each of us describes losing a physician patient to suicide. We walk the attendees through the clinical details of assessment, treatment, and the aftermath of their deaths. We talk openly and frankly about our feelings, grief, outreach to colleagues and the family, and our own personal journeys of learning, growth, and healing. The clinician audience members give constructive feedback, and some share their own stories of losing patients to suicide. Like the day before, some psychiatrists are grieving the loss of a physician son or sibling to suicide. As mental health professionals, they suffer from an additional layer of failure and guilt that a loved one died “under their watch.”
• May 8: I rush across the Javits Center to catch the discussant for a concurrent symposium on physician burnout and depression. She foregoes any prepared remarks to share her previous 48 hours with the audience. She is the training director of the program that lost the second-year resident on May 5. She did not learn of the death until 24 hours later. We are all on the edge of our seats as we listen to this grieving, courageous woman, a seasoned psychiatrist and educator, who has been blindsided by this tragedy. She has not slept. She called all of her residents and broke the news personally as best she could. Aided by “After A Suicide: A Toolkit for Residency/Fellowship Programs” (American Foundation for Suicide Prevention), she and her colleagues instituted a plan of action and worked with administration and faculty. Her strength and commitment to the well-being of her trainees is palpable and magnanimous. When the session ends, many of us stand in line to give her a hug. It is a stark reminder of how many lives are affected when someone you know or care about takes his/her own life – and how, in the house of medicine, medical students and residents really are part of an institutional family.
• May 10: I facilitate a meeting of our 12 second-year residents, many of whom knew of or had met the resident who died. Almost everyone speaks, shares their feelings, poses questions, and calls for answers and change. There is disbelief, sadness, confusion, some guilt, and lots of anger. Also a feeling of disillusionment or paradox about the field of psychiatry: “Of all branches of medicine, shouldn’t residents who are struggling with psychiatric issues feel safe, protected, cared for in psychiatry?” There is also a feeling of lip service being paid to personal treatment, as in quoted statements: “By all means, get treatment for your issues, but don’t let it encroach on your duty hours” or “It’s good you’re getting help, but do you still have to go weekly?”

 

In the immediate aftermath of suicide, feelings run high, as they should. But rather than wait it out – and fearing a return to “business as usual” – let me make only two suggestions:

1. We need to come together and talk about this – medical students and residents and training directors and deans. A town hall forum would be ideal. Although there are amazing innovations on wellness emanating from the Association of American Medical Colleges and Accreditation Council for Graduate Medical Education, many current medical students and residents feel frustrated – “This is taking too long” or “This is top down and being imposed on us” or “What about our voices … don’t they count?” Although students and residents have representatives on faculty committees, feedback is not universal, and not all residents believe that their senior peers truly convey their concerns to those in power. They want to be present at the table and speak for themselves. Too many do not feel they have a voice.

2. In psychiatry, we need to redouble our efforts in fighting the stigma attached to psychiatric illness in trainees. It is unconscionable that medical students and residents are dying of treatable disorders (I’ve never heard of a doctor dying of cancer who didn’t go to an oncologist at least once), yet too many are not availing themselves of services we provide – even when they’re free of charge or covered by insurance. And are we certain that, when they knock on our doors, we are providing them with state-of-the-art care? Is it possible that unrecognized internal stigma and shame deep within us might make us hesitant to help our trainees in their hour of need? Or cut corners? Or not get a second opinion? Very few psychiatrists on faculty of our medical schools divulge their personal experiences of depression, posttraumatic stress disorders, substance use disorders, and more (with the exception of being in therapy during residency, which is normative and isn’t stigmatized). Coming out is leveling, humane, and respectful – and it shrinks the power differential in the teaching dyad. It might even save a life.
 

Dr. Myers is a professor of clinical psychiatry at State University of New York, Brooklyn, and the author of “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared.”
 

Many of you reading this column joined Medicare accountable care organizations (ACOs) sometime between 2011 and 2016. As the power of prevention, wellness, and the medical home model are starting to be realized and appreciated, those benefits may be swamped by two new Centers for Medicare and Medicaid Services value-based revenue streams that did not exist when many of you first joined your ACO.

The Medicare Access and CHIP Reauthorization Act (MACRA) was passed in 2015 and is just now being implemented. Value-based, fee-for-service payments started out rather modestly a few years ago as chronic care management codes, but they have exploded to include more than 20 codes, counting the new ones coming online in 2018. Let’s call them collectively value-based care codes, or VCCs.

Even better, the proactive and coordinated care called for to succeed under MACRA and the VCCs will also drive higher quality scores and shared savings distributions for ACOs that incorporate them. There is opportunity to leverage all three of these revenue streams collectively using your ACO’s chassis.

Many practices are trying to understand and perform the basic requirements to avoid penalties under MACRA’s Merit-based Incentive Payment System (MIPS) program. Some primary care practices, however, see the upside potential and bonuses stacking up to 30% or more.

Did you know that even if you are in, let’s say, a basic Medicare Shared Savings Program ACO – the MSSP Track 1, with no exposure to risk – you get special treatment on reporting under MACRA as a MIPS Advanced Practice Model (APM)?

But more importantly, MACRA is a team game. Getting into an MSSP Track 1 is justified just to get practice for the care coordination you’ll need. Few physicians know that they are judged under MACRA MIPS for the total costs of their patients, not just their own costs. A primary care physician receives only up to 8% of the $10 million your patients consume on average. The best way to counter that is through an ACO.

Further, we are aware of ACOs that have chosen risk-taking Medicare models such as NextGen, even though they predict small losses. Those losses are because of the automatic 5% fee-for-service payment bump to its physicians for risk taking if they are in a MACRA Advanced Alternative Payment Model (AAPM).

 

There’s a wide range of primary care physicians who are seizing opportunities offered by VCCs.

A family physician friend of mine who practices in a rural area generated more than 50% of his revenue from value-based care coding last year. And he has personally generated more than $350,000 in additional annual revenue, not counting the revenue from additional medically necessary procedures revealed by this more proactive wellness assessment activity and early diagnoses.

On the other hand, because busy physicians have a hard time wading through all these regulations and implementing the required staff and technology changes, it is reported that only about 8% of physicians are employing even the chronic care management codes. And when they do, they only achieve an 18% eligible patient penetration. My friend has broken the code, so to speak; he has protocolized and templated the process, has happy patients, has an ongoing 93% penetration rate, and actually has more free time.

While you are busy saving lives, I have had the luxury of looking from a high level at these tectonic, value-based payment shifts. To me, it’s a no-brainer for a primary care physician to leverage their ACO to maximize all three revenue streams. Look at MACRA MIPS, MIPS-APM, and AAPM measures anew, and see how well they play into integrated care.

 

As quarterback of health care through the patient-centered medical home, you are in great position to drive substantial bonuses. Similarly, when one looks at VCCs, the ACO can: help you navigate through the paperwork, perform much of the required reporting, and select the highest value-adding initiatives to monitor and drive higher quality and shared savings for the ACO.

As readers know, we firmly believe that, to have sustained incentivization, every ACO needs to have a merit-based, shared savings distribution formula. Accordingly, your compensation should rise under MACRA, VCCs, and the ACO.

This shift to value care is hard. But your colleagues who have made these changes are enjoying practice as never before. Their professional and financial rewards have climbed. But, most important, their patients love it.

Mr. Bobbitt is head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of Value Health Partners, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

Many of you reading this column joined Medicare accountable care organizations (ACOs) sometime between 2011 and 2016. As the power of prevention, wellness, and the medical home model are starting to be realized and appreciated, those benefits may be swamped by two new Centers for Medicare and Medicaid Services value-based revenue streams that did not exist when many of you first joined your ACO.

The Medicare Access and CHIP Reauthorization Act (MACRA) was passed in 2015 and is just now being implemented. Value-based, fee-for-service payments started out rather modestly a few years ago as chronic care management codes, but they have exploded to include more than 20 codes, counting the new ones coming online in 2018. Let’s call them collectively value-based care codes, or VCCs.

Even better, the proactive and coordinated care called for to succeed under MACRA and the VCCs will also drive higher quality scores and shared savings distributions for ACOs that incorporate them. There is opportunity to leverage all three of these revenue streams collectively using your ACO’s chassis.

Many practices are trying to understand and perform the basic requirements to avoid penalties under MACRA’s Merit-based Incentive Payment System (MIPS) program. Some primary care practices, however, see the upside potential and bonuses stacking up to 30% or more.

Did you know that even if you are in, let’s say, a basic Medicare Shared Savings Program ACO – the MSSP Track 1, with no exposure to risk – you get special treatment on reporting under MACRA as a MIPS Advanced Practice Model (APM)?

But more importantly, MACRA is a team game. Getting into an MSSP Track 1 is justified just to get practice for the care coordination you’ll need. Few physicians know that they are judged under MACRA MIPS for the total costs of their patients, not just their own costs. A primary care physician receives only up to 8% of the $10 million your patients consume on average. The best way to counter that is through an ACO.

Further, we are aware of ACOs that have chosen risk-taking Medicare models such as NextGen, even though they predict small losses. Those losses are because of the automatic 5% fee-for-service payment bump to its physicians for risk taking if they are in a MACRA Advanced Alternative Payment Model (AAPM).

 

There’s a wide range of primary care physicians who are seizing opportunities offered by VCCs.

A family physician friend of mine who practices in a rural area generated more than 50% of his revenue from value-based care coding last year. And he has personally generated more than $350,000 in additional annual revenue, not counting the revenue from additional medically necessary procedures revealed by this more proactive wellness assessment activity and early diagnoses.

On the other hand, because busy physicians have a hard time wading through all these regulations and implementing the required staff and technology changes, it is reported that only about 8% of physicians are employing even the chronic care management codes. And when they do, they only achieve an 18% eligible patient penetration. My friend has broken the code, so to speak; he has protocolized and templated the process, has happy patients, has an ongoing 93% penetration rate, and actually has more free time.

While you are busy saving lives, I have had the luxury of looking from a high level at these tectonic, value-based payment shifts. To me, it’s a no-brainer for a primary care physician to leverage their ACO to maximize all three revenue streams. Look at MACRA MIPS, MIPS-APM, and AAPM measures anew, and see how well they play into integrated care.

 

As quarterback of health care through the patient-centered medical home, you are in great position to drive substantial bonuses. Similarly, when one looks at VCCs, the ACO can: help you navigate through the paperwork, perform much of the required reporting, and select the highest value-adding initiatives to monitor and drive higher quality and shared savings for the ACO.

As readers know, we firmly believe that, to have sustained incentivization, every ACO needs to have a merit-based, shared savings distribution formula. Accordingly, your compensation should rise under MACRA, VCCs, and the ACO.

This shift to value care is hard. But your colleagues who have made these changes are enjoying practice as never before. Their professional and financial rewards have climbed. But, most important, their patients love it.

Mr. Bobbitt is head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of Value Health Partners, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

Many of you reading this column joined Medicare accountable care organizations (ACOs) sometime between 2011 and 2016. As the power of prevention, wellness, and the medical home model are starting to be realized and appreciated, those benefits may be swamped by two new Centers for Medicare and Medicaid Services value-based revenue streams that did not exist when many of you first joined your ACO.

The Medicare Access and CHIP Reauthorization Act (MACRA) was passed in 2015 and is just now being implemented. Value-based, fee-for-service payments started out rather modestly a few years ago as chronic care management codes, but they have exploded to include more than 20 codes, counting the new ones coming online in 2018. Let’s call them collectively value-based care codes, or VCCs.

Even better, the proactive and coordinated care called for to succeed under MACRA and the VCCs will also drive higher quality scores and shared savings distributions for ACOs that incorporate them. There is opportunity to leverage all three of these revenue streams collectively using your ACO’s chassis.

Many practices are trying to understand and perform the basic requirements to avoid penalties under MACRA’s Merit-based Incentive Payment System (MIPS) program. Some primary care practices, however, see the upside potential and bonuses stacking up to 30% or more.

Did you know that even if you are in, let’s say, a basic Medicare Shared Savings Program ACO – the MSSP Track 1, with no exposure to risk – you get special treatment on reporting under MACRA as a MIPS Advanced Practice Model (APM)?

But more importantly, MACRA is a team game. Getting into an MSSP Track 1 is justified just to get practice for the care coordination you’ll need. Few physicians know that they are judged under MACRA MIPS for the total costs of their patients, not just their own costs. A primary care physician receives only up to 8% of the $10 million your patients consume on average. The best way to counter that is through an ACO.

Further, we are aware of ACOs that have chosen risk-taking Medicare models such as NextGen, even though they predict small losses. Those losses are because of the automatic 5% fee-for-service payment bump to its physicians for risk taking if they are in a MACRA Advanced Alternative Payment Model (AAPM).

 

There’s a wide range of primary care physicians who are seizing opportunities offered by VCCs.

A family physician friend of mine who practices in a rural area generated more than 50% of his revenue from value-based care coding last year. And he has personally generated more than $350,000 in additional annual revenue, not counting the revenue from additional medically necessary procedures revealed by this more proactive wellness assessment activity and early diagnoses.

On the other hand, because busy physicians have a hard time wading through all these regulations and implementing the required staff and technology changes, it is reported that only about 8% of physicians are employing even the chronic care management codes. And when they do, they only achieve an 18% eligible patient penetration. My friend has broken the code, so to speak; he has protocolized and templated the process, has happy patients, has an ongoing 93% penetration rate, and actually has more free time.

While you are busy saving lives, I have had the luxury of looking from a high level at these tectonic, value-based payment shifts. To me, it’s a no-brainer for a primary care physician to leverage their ACO to maximize all three revenue streams. Look at MACRA MIPS, MIPS-APM, and AAPM measures anew, and see how well they play into integrated care.

 

As quarterback of health care through the patient-centered medical home, you are in great position to drive substantial bonuses. Similarly, when one looks at VCCs, the ACO can: help you navigate through the paperwork, perform much of the required reporting, and select the highest value-adding initiatives to monitor and drive higher quality and shared savings for the ACO.

As readers know, we firmly believe that, to have sustained incentivization, every ACO needs to have a merit-based, shared savings distribution formula. Accordingly, your compensation should rise under MACRA, VCCs, and the ACO.

This shift to value care is hard. But your colleagues who have made these changes are enjoying practice as never before. Their professional and financial rewards have climbed. But, most important, their patients love it.

Mr. Bobbitt is head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of Value Health Partners, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

 

I’m about to embark on a controversial topic. Perhaps it’s safer to avoid, but I can’t put it off any longer. We need to talk about diet.

Discussing diet, like politics, religion, or salary, is best done just with oneself. Yet, I’m compelled to share what I’ve learned. First, I’m agnostic. I don’t believe you need to be vegan or paleo to be saved. I eat plant-based foods. I also eat things that eat plants. I’m sure you’d find a fine film of gluten in my kitchen. What I’ve learned is that for me, it doesn’t matter.

baibaz/iStock/Getty Images

You might approach diet in a strictly pragmatic way: food-as-fuel-to-burn to stay alive and see patients. You might also approach it as an essential component of a happy life, one where food is a core life pleasure and should be savored with others. As a pragmatist and an Italian-American, it is both for me.

The diet that I have found most helpful is one that depends upon the day of the week. Mondays through Thursdays, I fast. Specifically, I have little or nothing to eat from when I wake until dinner. As a busy dermatologist, that may seem draconian, but in fact it is easier than you might think. Patients are a constant all day, while hunger is fleeting. Got a craving at 10:15 a.m.? Easy. Walk in to see the next patient. Then repeat. Most days, this continues until 6:30 p.m. or so, when it’s time to head home. It’s not that hard, particularly when you don’t have anything in your office to eat except Dentyne Ice gum and green tea.

Now, this doesn’t always work. Why? Meetings. How do I manage fasting on those days? I don’t. If I know I have a lunch meeting scheduled, then I eat a healthy breakfast before I leave home, such as a protein smoothie or a bowl of hot oats with a dollop of Greek yogurt, sunflower seeds, walnuts, and berries. By eating a wholesome, well-balanced meal of fiber, carbs, lean protein, and good fats, I’m not starving before the meeting and am less likely to overeat. (That’s because I have also learned I’m not one of those enviable people who can simply say “no” to a crispy fish taco and guacamole if I’m hungry. I’m gonna eat it.) So, I avoid fasting and the inevitable frustration of breaking a fast on those days.

On days when I fast, I monitor how I feel. Fortunately, I have rarely felt hypoglycemic; except for that one Tuesday a couple of months ago. I had completed a long, hard early morning workout, and by mid-morning my hands were shaking and I felt nauseous. I quickly downed two RX bars and felt fine within minutes. Better for me, better for my patients.

Right now, intermittent fasting is working for me. Here’s my weekly plan:

 

Mondays through Thursdays I fast. I have coffee with plant-based milk in the morning and don’t eat anything else until dinner. On those days, dinner is usually salad with a protein, most often fish, that is approximately 500 calories. Sometimes we have pasta or a curry, but they’re made from scratch with seasonal, whole foods. I avoid eating dinner after 8 p.m. as it tends to disrupt my sleep.

I don’t fast on Fridays or weekends or when I travel. I eat out rarely. On weekends, my wife and I shop at the local farmers’ and fish markets to prepare ourselves for a week of healthy eating. And on Sundays, we continue our treasured family tradition of Sunday supper, which is basted with nostalgia and drizzled liberally with comfort. Often it requires long preparation, which is part of the appeal, and short attention is paid to its nutritional value. That’s not the point of Sunday dinner. A delicious dunk of fresh Italian bread in grassy-green olive oil or fresh pasta doused with homemade tomato basil sauce is the best possible meal I can have to prepare for a long, hard week ahead.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

 

I’m about to embark on a controversial topic. Perhaps it’s safer to avoid, but I can’t put it off any longer. We need to talk about diet.

Discussing diet, like politics, religion, or salary, is best done just with oneself. Yet, I’m compelled to share what I’ve learned. First, I’m agnostic. I don’t believe you need to be vegan or paleo to be saved. I eat plant-based foods. I also eat things that eat plants. I’m sure you’d find a fine film of gluten in my kitchen. What I’ve learned is that for me, it doesn’t matter.

baibaz/iStock/Getty Images

You might approach diet in a strictly pragmatic way: food-as-fuel-to-burn to stay alive and see patients. You might also approach it as an essential component of a happy life, one where food is a core life pleasure and should be savored with others. As a pragmatist and an Italian-American, it is both for me.

The diet that I have found most helpful is one that depends upon the day of the week. Mondays through Thursdays, I fast. Specifically, I have little or nothing to eat from when I wake until dinner. As a busy dermatologist, that may seem draconian, but in fact it is easier than you might think. Patients are a constant all day, while hunger is fleeting. Got a craving at 10:15 a.m.? Easy. Walk in to see the next patient. Then repeat. Most days, this continues until 6:30 p.m. or so, when it’s time to head home. It’s not that hard, particularly when you don’t have anything in your office to eat except Dentyne Ice gum and green tea.

Now, this doesn’t always work. Why? Meetings. How do I manage fasting on those days? I don’t. If I know I have a lunch meeting scheduled, then I eat a healthy breakfast before I leave home, such as a protein smoothie or a bowl of hot oats with a dollop of Greek yogurt, sunflower seeds, walnuts, and berries. By eating a wholesome, well-balanced meal of fiber, carbs, lean protein, and good fats, I’m not starving before the meeting and am less likely to overeat. (That’s because I have also learned I’m not one of those enviable people who can simply say “no” to a crispy fish taco and guacamole if I’m hungry. I’m gonna eat it.) So, I avoid fasting and the inevitable frustration of breaking a fast on those days.

On days when I fast, I monitor how I feel. Fortunately, I have rarely felt hypoglycemic; except for that one Tuesday a couple of months ago. I had completed a long, hard early morning workout, and by mid-morning my hands were shaking and I felt nauseous. I quickly downed two RX bars and felt fine within minutes. Better for me, better for my patients.

Right now, intermittent fasting is working for me. Here’s my weekly plan:

 

Mondays through Thursdays I fast. I have coffee with plant-based milk in the morning and don’t eat anything else until dinner. On those days, dinner is usually salad with a protein, most often fish, that is approximately 500 calories. Sometimes we have pasta or a curry, but they’re made from scratch with seasonal, whole foods. I avoid eating dinner after 8 p.m. as it tends to disrupt my sleep.

I don’t fast on Fridays or weekends or when I travel. I eat out rarely. On weekends, my wife and I shop at the local farmers’ and fish markets to prepare ourselves for a week of healthy eating. And on Sundays, we continue our treasured family tradition of Sunday supper, which is basted with nostalgia and drizzled liberally with comfort. Often it requires long preparation, which is part of the appeal, and short attention is paid to its nutritional value. That’s not the point of Sunday dinner. A delicious dunk of fresh Italian bread in grassy-green olive oil or fresh pasta doused with homemade tomato basil sauce is the best possible meal I can have to prepare for a long, hard week ahead.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

 

I’m about to embark on a controversial topic. Perhaps it’s safer to avoid, but I can’t put it off any longer. We need to talk about diet.

Discussing diet, like politics, religion, or salary, is best done just with oneself. Yet, I’m compelled to share what I’ve learned. First, I’m agnostic. I don’t believe you need to be vegan or paleo to be saved. I eat plant-based foods. I also eat things that eat plants. I’m sure you’d find a fine film of gluten in my kitchen. What I’ve learned is that for me, it doesn’t matter.

baibaz/iStock/Getty Images

You might approach diet in a strictly pragmatic way: food-as-fuel-to-burn to stay alive and see patients. You might also approach it as an essential component of a happy life, one where food is a core life pleasure and should be savored with others. As a pragmatist and an Italian-American, it is both for me.

The diet that I have found most helpful is one that depends upon the day of the week. Mondays through Thursdays, I fast. Specifically, I have little or nothing to eat from when I wake until dinner. As a busy dermatologist, that may seem draconian, but in fact it is easier than you might think. Patients are a constant all day, while hunger is fleeting. Got a craving at 10:15 a.m.? Easy. Walk in to see the next patient. Then repeat. Most days, this continues until 6:30 p.m. or so, when it’s time to head home. It’s not that hard, particularly when you don’t have anything in your office to eat except Dentyne Ice gum and green tea.

Now, this doesn’t always work. Why? Meetings. How do I manage fasting on those days? I don’t. If I know I have a lunch meeting scheduled, then I eat a healthy breakfast before I leave home, such as a protein smoothie or a bowl of hot oats with a dollop of Greek yogurt, sunflower seeds, walnuts, and berries. By eating a wholesome, well-balanced meal of fiber, carbs, lean protein, and good fats, I’m not starving before the meeting and am less likely to overeat. (That’s because I have also learned I’m not one of those enviable people who can simply say “no” to a crispy fish taco and guacamole if I’m hungry. I’m gonna eat it.) So, I avoid fasting and the inevitable frustration of breaking a fast on those days.

On days when I fast, I monitor how I feel. Fortunately, I have rarely felt hypoglycemic; except for that one Tuesday a couple of months ago. I had completed a long, hard early morning workout, and by mid-morning my hands were shaking and I felt nauseous. I quickly downed two RX bars and felt fine within minutes. Better for me, better for my patients.

Right now, intermittent fasting is working for me. Here’s my weekly plan:

 

Mondays through Thursdays I fast. I have coffee with plant-based milk in the morning and don’t eat anything else until dinner. On those days, dinner is usually salad with a protein, most often fish, that is approximately 500 calories. Sometimes we have pasta or a curry, but they’re made from scratch with seasonal, whole foods. I avoid eating dinner after 8 p.m. as it tends to disrupt my sleep.

I don’t fast on Fridays or weekends or when I travel. I eat out rarely. On weekends, my wife and I shop at the local farmers’ and fish markets to prepare ourselves for a week of healthy eating. And on Sundays, we continue our treasured family tradition of Sunday supper, which is basted with nostalgia and drizzled liberally with comfort. Often it requires long preparation, which is part of the appeal, and short attention is paid to its nutritional value. That’s not the point of Sunday dinner. A delicious dunk of fresh Italian bread in grassy-green olive oil or fresh pasta doused with homemade tomato basil sauce is the best possible meal I can have to prepare for a long, hard week ahead.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].