For Residents

Case Presentation. A 64-year-old US Army veteran with a history of colorectal cancer, melanoma, and fibrinolytic presented with dyspnea to VA Boston Healthcare System (VABHS). Seven years prior to the current presentation, at the time of her diagnosis of colorectal cancer, the patient was found to be HIV negative but to have a positive purified protein derivative (PPD) test. She was treated with isoniazid (INH) therapy for 9 months. Sputum cultures collected prior to initiation of therapy grew Mycobacterium avium complex (MAC) in 1 of 3 samples, with these results reported several months after initiation of therapy. She was a never smoker with no known travel or exposure. At the time of the current presentation, her medications included bupropion, levothyroxine, capsaicin, cyclobenzaprine, ibuprofen, and acetaminophen.

►Lakshmana Swamy, MD, Chief Medical Resident, VABHS and Boston Medical Center. Dr. Monach, this patient is on a variety of pain medications and has a diagnosis of fibromyalgia. This diagnosis often frustrates doctors and patients alike. Can you tell us about fibromyalgia from the rheumatologist’s perspective and what you think of her current treatment regimen?

►Paul A. Monach, MD, PhD, Chief, Section of Rheumatology, VABHS and Associate Professor of Medicine, Boston University School of Medicine. Fibromyalgia is a syndrome of chronic widespread pain without known pathology in the musculoskeletal system. It is thought to be caused by chronic dysfunction of pain-processing pathways in the central nervous system (CNS). It is often accompanied by other somatic symptoms such as chronic fatigue, irritable bowel syndrome, and bladder pain. It is a common condition, affecting up to 5% of otherwise healthy women. It is particularly common in persons with chronic nonrestorative sleep or posttraumatic stress disorder from a wide range of causes. However, it also is more common in persons with autoimmune inflammatory diseases, such as lupus, Sjögren syndrome, or rheumatoid arthritis. Concern for one of these diseases is the main reason to consider referring a patient for evaluation by a rheumatologist. Often rheumatologists participate in the management of fibromyalgia. A patient should be given appropriate expectations by the referring physician.

Effectiveness of treatment varies widely among patients. Nonpharmacologic approaches such as aerobic exercise, cognitive behavioral therapy, and tai chi have support from clinical trials, and yoga and aquatherapy also are widely used.^1,2 The classes of drugs used are the same as for neuropathic pain: tricyclics, including cyclobenzaprine; serotonin and norepinephrine reuptake inhibitors (SNRIs); and gabapentinoids. In contrast, nonsteroidal anti-inflammatory drugs and opioids are ineffective unless there is a superimposed mechanical or inflammatory cause in the periphery. The key point is that continuation of any treatment should be based entirely on the patient’s own assessment of benefit.

►Dr. Swamy. Seven years later, the patient returned to her primary care provider, reporting increased dyspnea on exertion as well as significant fatigue. She was referred to the pulmonary department and had repeat computed tomography (CT) scans of the chest, which indicated persistent right middle lobe (RML) bronchiectasis. She then underwent bronchoscopy with a subsequent bronchoalveolar lavage (BAL) culture growing MAC. Dr. Fine, please interpret the baseline and follow-up CT scans and help us understand the significance of the MAC on sputum and BAL cultures.

►Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine. Prior to this presentation, the patient had a pleural-based area of fibrosis with possible associated RML bronchiectasis. This appears to be a postinflammatory process without classic features of malignant or metastatic disease. She then had a sputum, which grew MAC in only 1 of 3 samples and in liquid media only. Importantly, the sputum was not smear positive. All of this suggests a low organism burden. One possibility is that this could reflect colonization with MAC; it is not uncommon for patients with underlying chronic changes in their lung to grow MAC, and it is often difficult to tell whether it is indicative of active disease. Structural lung disease, such as bronchiectasis, predisposes a patient to MAC, but chronic MAC also may cause bronchiectasis. This chicken-and-egg scenario comes up frequently. She may have a MAC infection, but as she is HIV negative and asymptomatic, there is no urgent indication to treat, especially as the burden of therapy is not insignificant.

►Dr. Swamy. Do we need to worry about Mycobacterium tuberculosis (MTB)?

►Dr. Fine. Although she was previously PPD positive, she had already completed 1 year of isoniazid (INH) therapy, making active MTB less likely. From an infection control standpoint, it is important to distinguish MAC from MTB. The former is not contagious, and there is no need for airborne isolation.

►Dr. Swamy. Dr. Fine, where does MAC come from? Does it commonly cause disease?

►Dr. Fine. In the environment, MAC is nearly ubiquitous , especially in water and soil. In one study, 20% of showerheads were positive for MAC; when patients are infected, we may suggest changing/bleaching the showerhead, but there are no definitive recommendations.³ Because MAC is so common in the environment, it is unlikely that measures to target MAC colonization will be clinically meaningful. On the other hand, the incidence of nontuberculous mycobacterial infections is increasing across the US, and it may be a common and frequently underdiagnosed cause of chronic cough, especially in postmenopausal women.

►Dr. Swamy. Four years prior to the current presentation, the patient developed a cough after an upper respiratory tract infection that persisted for more than 2 weeks. Given her history, she underwent a repeat chest CT, which noted a slight increase in nodularity and ground-glass opacity restricted to the RML. She also reported dyspnea on exertion and was referred to the pulmonary medicine department. By the time she arrived, her dyspnea had largely resolved, but she reported persistent fatigue without other systemic symptoms, such as fevers or chills. Dr. Fine, does MAC explain this patient’s dyspnea?

►Dr. Fine. As her pulmonary symptoms resolved in a short period of time with only azithromycin, it is very unlikely that her symptoms were related to her prior disease. The MAC infection is not likely to cause dyspnea on exertion and fatigue and should be worked up more broadly before attributing it to MAC. In view of this, it would not be unreasonable to follow her clinically and see her again in 6 to 8 weeks. In this context, we also should consider the untoward impact of repeated radiation exposure derived from multiple CT scans. When a patient has an abnormality on CT scan, it often leads to further scans even if the symptoms do not match the previous findings, as in this case.

►Dr. Swamy. Given her ongoing fatigue and systemic symptoms (morning stiffness of the shoulders, legs, and thighs, and leg cramps), she was referred to the rheumatology department where the physical examination revealed muscle tenderness in her proximal arms and legs with normal strength, tender points at the elbows and medial side of the bilateral knees, significant tenderness of lower legs, and no synovitis.

Dr. Monach, can you walk us through your approach to this patient? Are we seeing manifestations of fibromyalgia? What diagnoses concerns you and how would you proceed?

►Dr. Monach. The history and exam are most helpful in raising or reducing suspicion for an underlying inflammatory disease. Areas of tenderness described in her case are typical of fibromyalgia, although it can be difficult to interpret symptoms in the hip girdle and shoulder girdle because objective findings are often absent on exam in patients with inflammatory arthritis or bursitis. Similarly, tenderness at sites of tendon insertion (enthuses) without objective abnormalities is common in different forms of spondyloarthritis, so tenderness at the elbow, knee, lateral hip, and low back can be difficult to interpret. What this patient is lacking is prominent subjective or objective findings in the joints most commonly affected in rheumatoid arthritis and lupus: wrists, hands, ankles, and feet.

►Dr. Swamy. Initial laboratory data include an erythrocyte sedimentation rate of 79 with a normal C-reactive protein. A tentative diagnosis of polymyalgia rheumatic is made with consideration of a trial treatment of prednisone.

Dr. Monach, this patient has an indolent infection and is about to be given glucocorticoids. Could you describe the situations in which you feel that glucocorticoids cause a relative immunosuppression?

►Dr. Monach. Glucocorticoids are considered safe in a patient whose infection is not intrinsically dangerous or who has started appropriate antibiotics for that infection. Although all toxicities of glucocorticoids are dose dependent, the long-standing assertion that doses below 10 mg to 15 mg do not increase risk of infection is contradicted by data published in the past 10 to 15 years, with the caveat that these patients were on long-term treatment.

►Dr. Swamy. The patient was started on prednisone 15 mg per day for 15 days. She returned to the clinic after 1 week of prednisone troutment and noted “significant improvement in fatigue, morning stiffness of shoulders, thighs, leg, back is better, leg cramps resolved, shooting pain in many joints resolved.” Further laboratory results were notable for a negative rheumatoid factor, negative antinuclear antibody, and a cyclic citrullinated peptide of 60. A presumptive diagnosis of rheumatoid arthritis (RA) was made and plaquenil 200 mg twice daily was started.

Dr. Monach, can you explain why RA comes up now on serology but was not considered initially? Why does this presentation fit RA, and was her response to treatment typical? How does this fit in with her previous diagnosis of fibromyalgia? Was that just an atypical, indolent presentation of RA?

►Dr. Monach. Though her presentation is atypical for RA, in elderly patients, RA can present with symptoms resembling polymyalgia rheumatica. The question is whether she had RA all along (in which case “elderly onset” would not apply) or had fibromyalgia and developed RA more recently. The response to empiric glucocorticoid therapy is helpful, since fibromyalgia should not improve with prednisone even in a patient with RA unless treatment of RA would allow better sleep and ability to exercise. Rheumatoid arthritis typically responds very well to prednisone in the 5-mg to 15-mg range.

►Dr. Swamy. Given the new diagnosis of an inflammatory arthritis requiring immunosuppression, bronchoscopy with BAL is performed to evaluate for the presence of MAC. These cultures were positive for MAC.

Dr. Fine, does the positive BAL culture indicate an active MAC infection?

►Dr. Fine. Yes, based on these updated data, the patient has an active MAC infection. Active infection is defined as symptoms or imaging consistent with the diagnosis, supporting microbiology data (either 2 sputum or 1 BAL sample growing MAC) and the exclusion of other causes. Previously, this patient grew MAC in just one expectorated sputum; this did not meet the microbiologic criteria. Now sputum has grown in the BAL sample; along with the CT imaging, this is enough to diagnosis active MAC infection.

Treatment for MAC must consider the details of each case. First, this is not an emergency; treatment decisions should be made with the rheumatologist to consider the planned immunosuppression. For example, we must consider potential drug interactions. A specific point should be made of the use of tumor necrosis factor (TNF)-α inhibition, which data indicate can reactivate TB and may inhibit mechanisms that restrain mycobacterial disease. Serious cases of MAC infection have been reported in the literature in the setting of TNF-α inhibition.^5,6 Despite these concerns, there is not a contraindication to using these therapies from the perspective of the active MAC disease. All of these decisions will impact the need to commit the patient to MAC therapy.

►Dr. Swamy. Dr. Fine, what do you consider prior to initiating MAC therapy?

► Dr. Fine. The decision to pursue MAC therapy should not be taken lightly. Therapy often entails prolonged multidrug regimens, usually spanning more than a year, with frequent adverse effects. Outside of very specific cases, such as TNF-β inhibition, MAC is rarely a life-threatening disease, so the benefit may be limited. Treatment for MAC is certainly unlikely to be fruitful without a diligent and motivated patient able to handle the high and prolonged pill burden. Of note, it is also important to keep this patient up-to-date with influenza and pneumonia vaccination given her structural lung disease.

►Dr. Swamy. The decision is made to treat MAC with azithromycin, rifampin, and ethambutol. The disease is noted to be nonfibrocavitary. The patient underwent monthly liver function test monitoring and visual acuity testing, which were unremarkable. Dr. Fine, can you describe the phenotypes of nontuberculous mycobacterial (NTM) disease?

►Dr. Fine. There are 3 main phenotypes of NTM.³ First, we see the elderly man with preexisting lung disease—usually chronic obstructive pulmonary disease—with fibrocavitary and/or reticulonodular appearance. Second, we see the slim, elderly woman often without any preexisting lung disease presenting with focal bronchiectasis and nodular lesions in right middle lobe and lingula—the Lady Windermere syndrome. This eponym is derived from Oscar Wilde’s play “Lady Windermere’s Fan, a Play About a Good Woman,” and was first associated with this disease in 1992.⁷ At the time, it was thought that the voluntary suppression of cough led to poorly draining lung regions, vulnerable to engraftment by atypical mycobacteria. Infection with atypical mycobacteria are associated with this population; however, it is no longer thought to be due to the voluntary suppression of cough.^7,8 Third, we do occasionally see atypical presentations, such as focal masses and solitary nodules.

►Dr. Swamy. At 1-year follow-up she successfully completed MAC therapy and noted ongoing control of rheumatoid symptoms.

Case Presentation. A 64-year-old US Army veteran with a history of colorectal cancer, melanoma, and fibrinolytic presented with dyspnea to VA Boston Healthcare System (VABHS). Seven years prior to the current presentation, at the time of her diagnosis of colorectal cancer, the patient was found to be HIV negative but to have a positive purified protein derivative (PPD) test. She was treated with isoniazid (INH) therapy for 9 months. Sputum cultures collected prior to initiation of therapy grew Mycobacterium avium complex (MAC) in 1 of 3 samples, with these results reported several months after initiation of therapy. She was a never smoker with no known travel or exposure. At the time of the current presentation, her medications included bupropion, levothyroxine, capsaicin, cyclobenzaprine, ibuprofen, and acetaminophen.

►Lakshmana Swamy, MD, Chief Medical Resident, VABHS and Boston Medical Center. Dr. Monach, this patient is on a variety of pain medications and has a diagnosis of fibromyalgia. This diagnosis often frustrates doctors and patients alike. Can you tell us about fibromyalgia from the rheumatologist’s perspective and what you think of her current treatment regimen?

►Paul A. Monach, MD, PhD, Chief, Section of Rheumatology, VABHS and Associate Professor of Medicine, Boston University School of Medicine. Fibromyalgia is a syndrome of chronic widespread pain without known pathology in the musculoskeletal system. It is thought to be caused by chronic dysfunction of pain-processing pathways in the central nervous system (CNS). It is often accompanied by other somatic symptoms such as chronic fatigue, irritable bowel syndrome, and bladder pain. It is a common condition, affecting up to 5% of otherwise healthy women. It is particularly common in persons with chronic nonrestorative sleep or posttraumatic stress disorder from a wide range of causes. However, it also is more common in persons with autoimmune inflammatory diseases, such as lupus, Sjögren syndrome, or rheumatoid arthritis. Concern for one of these diseases is the main reason to consider referring a patient for evaluation by a rheumatologist. Often rheumatologists participate in the management of fibromyalgia. A patient should be given appropriate expectations by the referring physician.

Effectiveness of treatment varies widely among patients. Nonpharmacologic approaches such as aerobic exercise, cognitive behavioral therapy, and tai chi have support from clinical trials, and yoga and aquatherapy also are widely used.^1,2 The classes of drugs used are the same as for neuropathic pain: tricyclics, including cyclobenzaprine; serotonin and norepinephrine reuptake inhibitors (SNRIs); and gabapentinoids. In contrast, nonsteroidal anti-inflammatory drugs and opioids are ineffective unless there is a superimposed mechanical or inflammatory cause in the periphery. The key point is that continuation of any treatment should be based entirely on the patient’s own assessment of benefit.

►Dr. Swamy. Seven years later, the patient returned to her primary care provider, reporting increased dyspnea on exertion as well as significant fatigue. She was referred to the pulmonary department and had repeat computed tomography (CT) scans of the chest, which indicated persistent right middle lobe (RML) bronchiectasis. She then underwent bronchoscopy with a subsequent bronchoalveolar lavage (BAL) culture growing MAC. Dr. Fine, please interpret the baseline and follow-up CT scans and help us understand the significance of the MAC on sputum and BAL cultures.

►Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine. Prior to this presentation, the patient had a pleural-based area of fibrosis with possible associated RML bronchiectasis. This appears to be a postinflammatory process without classic features of malignant or metastatic disease. She then had a sputum, which grew MAC in only 1 of 3 samples and in liquid media only. Importantly, the sputum was not smear positive. All of this suggests a low organism burden. One possibility is that this could reflect colonization with MAC; it is not uncommon for patients with underlying chronic changes in their lung to grow MAC, and it is often difficult to tell whether it is indicative of active disease. Structural lung disease, such as bronchiectasis, predisposes a patient to MAC, but chronic MAC also may cause bronchiectasis. This chicken-and-egg scenario comes up frequently. She may have a MAC infection, but as she is HIV negative and asymptomatic, there is no urgent indication to treat, especially as the burden of therapy is not insignificant.

►Dr. Swamy. Do we need to worry about Mycobacterium tuberculosis (MTB)?

►Dr. Fine. Although she was previously PPD positive, she had already completed 1 year of isoniazid (INH) therapy, making active MTB less likely. From an infection control standpoint, it is important to distinguish MAC from MTB. The former is not contagious, and there is no need for airborne isolation.

►Dr. Swamy. Dr. Fine, where does MAC come from? Does it commonly cause disease?

►Dr. Fine. In the environment, MAC is nearly ubiquitous , especially in water and soil. In one study, 20% of showerheads were positive for MAC; when patients are infected, we may suggest changing/bleaching the showerhead, but there are no definitive recommendations.³ Because MAC is so common in the environment, it is unlikely that measures to target MAC colonization will be clinically meaningful. On the other hand, the incidence of nontuberculous mycobacterial infections is increasing across the US, and it may be a common and frequently underdiagnosed cause of chronic cough, especially in postmenopausal women.

►Dr. Swamy. Four years prior to the current presentation, the patient developed a cough after an upper respiratory tract infection that persisted for more than 2 weeks. Given her history, she underwent a repeat chest CT, which noted a slight increase in nodularity and ground-glass opacity restricted to the RML. She also reported dyspnea on exertion and was referred to the pulmonary medicine department. By the time she arrived, her dyspnea had largely resolved, but she reported persistent fatigue without other systemic symptoms, such as fevers or chills. Dr. Fine, does MAC explain this patient’s dyspnea?

►Dr. Fine. As her pulmonary symptoms resolved in a short period of time with only azithromycin, it is very unlikely that her symptoms were related to her prior disease. The MAC infection is not likely to cause dyspnea on exertion and fatigue and should be worked up more broadly before attributing it to MAC. In view of this, it would not be unreasonable to follow her clinically and see her again in 6 to 8 weeks. In this context, we also should consider the untoward impact of repeated radiation exposure derived from multiple CT scans. When a patient has an abnormality on CT scan, it often leads to further scans even if the symptoms do not match the previous findings, as in this case.

►Dr. Swamy. Given her ongoing fatigue and systemic symptoms (morning stiffness of the shoulders, legs, and thighs, and leg cramps), she was referred to the rheumatology department where the physical examination revealed muscle tenderness in her proximal arms and legs with normal strength, tender points at the elbows and medial side of the bilateral knees, significant tenderness of lower legs, and no synovitis.

Dr. Monach, can you walk us through your approach to this patient? Are we seeing manifestations of fibromyalgia? What diagnoses concerns you and how would you proceed?

►Dr. Monach. The history and exam are most helpful in raising or reducing suspicion for an underlying inflammatory disease. Areas of tenderness described in her case are typical of fibromyalgia, although it can be difficult to interpret symptoms in the hip girdle and shoulder girdle because objective findings are often absent on exam in patients with inflammatory arthritis or bursitis. Similarly, tenderness at sites of tendon insertion (enthuses) without objective abnormalities is common in different forms of spondyloarthritis, so tenderness at the elbow, knee, lateral hip, and low back can be difficult to interpret. What this patient is lacking is prominent subjective or objective findings in the joints most commonly affected in rheumatoid arthritis and lupus: wrists, hands, ankles, and feet.

►Dr. Swamy. Initial laboratory data include an erythrocyte sedimentation rate of 79 with a normal C-reactive protein. A tentative diagnosis of polymyalgia rheumatic is made with consideration of a trial treatment of prednisone.

Dr. Monach, this patient has an indolent infection and is about to be given glucocorticoids. Could you describe the situations in which you feel that glucocorticoids cause a relative immunosuppression?

►Dr. Monach. Glucocorticoids are considered safe in a patient whose infection is not intrinsically dangerous or who has started appropriate antibiotics for that infection. Although all toxicities of glucocorticoids are dose dependent, the long-standing assertion that doses below 10 mg to 15 mg do not increase risk of infection is contradicted by data published in the past 10 to 15 years, with the caveat that these patients were on long-term treatment.

►Dr. Swamy. The patient was started on prednisone 15 mg per day for 15 days. She returned to the clinic after 1 week of prednisone troutment and noted “significant improvement in fatigue, morning stiffness of shoulders, thighs, leg, back is better, leg cramps resolved, shooting pain in many joints resolved.” Further laboratory results were notable for a negative rheumatoid factor, negative antinuclear antibody, and a cyclic citrullinated peptide of 60. A presumptive diagnosis of rheumatoid arthritis (RA) was made and plaquenil 200 mg twice daily was started.

Dr. Monach, can you explain why RA comes up now on serology but was not considered initially? Why does this presentation fit RA, and was her response to treatment typical? How does this fit in with her previous diagnosis of fibromyalgia? Was that just an atypical, indolent presentation of RA?

►Dr. Monach. Though her presentation is atypical for RA, in elderly patients, RA can present with symptoms resembling polymyalgia rheumatica. The question is whether she had RA all along (in which case “elderly onset” would not apply) or had fibromyalgia and developed RA more recently. The response to empiric glucocorticoid therapy is helpful, since fibromyalgia should not improve with prednisone even in a patient with RA unless treatment of RA would allow better sleep and ability to exercise. Rheumatoid arthritis typically responds very well to prednisone in the 5-mg to 15-mg range.

►Dr. Swamy. Given the new diagnosis of an inflammatory arthritis requiring immunosuppression, bronchoscopy with BAL is performed to evaluate for the presence of MAC. These cultures were positive for MAC.

Dr. Fine, does the positive BAL culture indicate an active MAC infection?

►Dr. Fine. Yes, based on these updated data, the patient has an active MAC infection. Active infection is defined as symptoms or imaging consistent with the diagnosis, supporting microbiology data (either 2 sputum or 1 BAL sample growing MAC) and the exclusion of other causes. Previously, this patient grew MAC in just one expectorated sputum; this did not meet the microbiologic criteria. Now sputum has grown in the BAL sample; along with the CT imaging, this is enough to diagnosis active MAC infection.

Treatment for MAC must consider the details of each case. First, this is not an emergency; treatment decisions should be made with the rheumatologist to consider the planned immunosuppression. For example, we must consider potential drug interactions. A specific point should be made of the use of tumor necrosis factor (TNF)-α inhibition, which data indicate can reactivate TB and may inhibit mechanisms that restrain mycobacterial disease. Serious cases of MAC infection have been reported in the literature in the setting of TNF-α inhibition.^5,6 Despite these concerns, there is not a contraindication to using these therapies from the perspective of the active MAC disease. All of these decisions will impact the need to commit the patient to MAC therapy.

►Dr. Swamy. Dr. Fine, what do you consider prior to initiating MAC therapy?

► Dr. Fine. The decision to pursue MAC therapy should not be taken lightly. Therapy often entails prolonged multidrug regimens, usually spanning more than a year, with frequent adverse effects. Outside of very specific cases, such as TNF-β inhibition, MAC is rarely a life-threatening disease, so the benefit may be limited. Treatment for MAC is certainly unlikely to be fruitful without a diligent and motivated patient able to handle the high and prolonged pill burden. Of note, it is also important to keep this patient up-to-date with influenza and pneumonia vaccination given her structural lung disease.

►Dr. Swamy. The decision is made to treat MAC with azithromycin, rifampin, and ethambutol. The disease is noted to be nonfibrocavitary. The patient underwent monthly liver function test monitoring and visual acuity testing, which were unremarkable. Dr. Fine, can you describe the phenotypes of nontuberculous mycobacterial (NTM) disease?

►Dr. Fine. There are 3 main phenotypes of NTM.³ First, we see the elderly man with preexisting lung disease—usually chronic obstructive pulmonary disease—with fibrocavitary and/or reticulonodular appearance. Second, we see the slim, elderly woman often without any preexisting lung disease presenting with focal bronchiectasis and nodular lesions in right middle lobe and lingula—the Lady Windermere syndrome. This eponym is derived from Oscar Wilde’s play “Lady Windermere’s Fan, a Play About a Good Woman,” and was first associated with this disease in 1992.⁷ At the time, it was thought that the voluntary suppression of cough led to poorly draining lung regions, vulnerable to engraftment by atypical mycobacteria. Infection with atypical mycobacteria are associated with this population; however, it is no longer thought to be due to the voluntary suppression of cough.^7,8 Third, we do occasionally see atypical presentations, such as focal masses and solitary nodules.

►Dr. Swamy. At 1-year follow-up she successfully completed MAC therapy and noted ongoing control of rheumatoid symptoms.

Case Presentation. A 64-year-old US Army veteran with a history of colorectal cancer, melanoma, and fibrinolytic presented with dyspnea to VA Boston Healthcare System (VABHS). Seven years prior to the current presentation, at the time of her diagnosis of colorectal cancer, the patient was found to be HIV negative but to have a positive purified protein derivative (PPD) test. She was treated with isoniazid (INH) therapy for 9 months. Sputum cultures collected prior to initiation of therapy grew Mycobacterium avium complex (MAC) in 1 of 3 samples, with these results reported several months after initiation of therapy. She was a never smoker with no known travel or exposure. At the time of the current presentation, her medications included bupropion, levothyroxine, capsaicin, cyclobenzaprine, ibuprofen, and acetaminophen.

►Lakshmana Swamy, MD, Chief Medical Resident, VABHS and Boston Medical Center. Dr. Monach, this patient is on a variety of pain medications and has a diagnosis of fibromyalgia. This diagnosis often frustrates doctors and patients alike. Can you tell us about fibromyalgia from the rheumatologist’s perspective and what you think of her current treatment regimen?

►Paul A. Monach, MD, PhD, Chief, Section of Rheumatology, VABHS and Associate Professor of Medicine, Boston University School of Medicine. Fibromyalgia is a syndrome of chronic widespread pain without known pathology in the musculoskeletal system. It is thought to be caused by chronic dysfunction of pain-processing pathways in the central nervous system (CNS). It is often accompanied by other somatic symptoms such as chronic fatigue, irritable bowel syndrome, and bladder pain. It is a common condition, affecting up to 5% of otherwise healthy women. It is particularly common in persons with chronic nonrestorative sleep or posttraumatic stress disorder from a wide range of causes. However, it also is more common in persons with autoimmune inflammatory diseases, such as lupus, Sjögren syndrome, or rheumatoid arthritis. Concern for one of these diseases is the main reason to consider referring a patient for evaluation by a rheumatologist. Often rheumatologists participate in the management of fibromyalgia. A patient should be given appropriate expectations by the referring physician.

Effectiveness of treatment varies widely among patients. Nonpharmacologic approaches such as aerobic exercise, cognitive behavioral therapy, and tai chi have support from clinical trials, and yoga and aquatherapy also are widely used.^1,2 The classes of drugs used are the same as for neuropathic pain: tricyclics, including cyclobenzaprine; serotonin and norepinephrine reuptake inhibitors (SNRIs); and gabapentinoids. In contrast, nonsteroidal anti-inflammatory drugs and opioids are ineffective unless there is a superimposed mechanical or inflammatory cause in the periphery. The key point is that continuation of any treatment should be based entirely on the patient’s own assessment of benefit.

►Dr. Swamy. Seven years later, the patient returned to her primary care provider, reporting increased dyspnea on exertion as well as significant fatigue. She was referred to the pulmonary department and had repeat computed tomography (CT) scans of the chest, which indicated persistent right middle lobe (RML) bronchiectasis. She then underwent bronchoscopy with a subsequent bronchoalveolar lavage (BAL) culture growing MAC. Dr. Fine, please interpret the baseline and follow-up CT scans and help us understand the significance of the MAC on sputum and BAL cultures.

►Alan Fine, MD, Section of Pulmonary and Critical Care, VABHS and Professor of Medicine, Boston University School of Medicine. Prior to this presentation, the patient had a pleural-based area of fibrosis with possible associated RML bronchiectasis. This appears to be a postinflammatory process without classic features of malignant or metastatic disease. She then had a sputum, which grew MAC in only 1 of 3 samples and in liquid media only. Importantly, the sputum was not smear positive. All of this suggests a low organism burden. One possibility is that this could reflect colonization with MAC; it is not uncommon for patients with underlying chronic changes in their lung to grow MAC, and it is often difficult to tell whether it is indicative of active disease. Structural lung disease, such as bronchiectasis, predisposes a patient to MAC, but chronic MAC also may cause bronchiectasis. This chicken-and-egg scenario comes up frequently. She may have a MAC infection, but as she is HIV negative and asymptomatic, there is no urgent indication to treat, especially as the burden of therapy is not insignificant.

►Dr. Swamy. Do we need to worry about Mycobacterium tuberculosis (MTB)?

►Dr. Fine. Although she was previously PPD positive, she had already completed 1 year of isoniazid (INH) therapy, making active MTB less likely. From an infection control standpoint, it is important to distinguish MAC from MTB. The former is not contagious, and there is no need for airborne isolation.

►Dr. Swamy. Dr. Fine, where does MAC come from? Does it commonly cause disease?

►Dr. Fine. In the environment, MAC is nearly ubiquitous , especially in water and soil. In one study, 20% of showerheads were positive for MAC; when patients are infected, we may suggest changing/bleaching the showerhead, but there are no definitive recommendations.³ Because MAC is so common in the environment, it is unlikely that measures to target MAC colonization will be clinically meaningful. On the other hand, the incidence of nontuberculous mycobacterial infections is increasing across the US, and it may be a common and frequently underdiagnosed cause of chronic cough, especially in postmenopausal women.

►Dr. Swamy. Four years prior to the current presentation, the patient developed a cough after an upper respiratory tract infection that persisted for more than 2 weeks. Given her history, she underwent a repeat chest CT, which noted a slight increase in nodularity and ground-glass opacity restricted to the RML. She also reported dyspnea on exertion and was referred to the pulmonary medicine department. By the time she arrived, her dyspnea had largely resolved, but she reported persistent fatigue without other systemic symptoms, such as fevers or chills. Dr. Fine, does MAC explain this patient’s dyspnea?

►Dr. Fine. As her pulmonary symptoms resolved in a short period of time with only azithromycin, it is very unlikely that her symptoms were related to her prior disease. The MAC infection is not likely to cause dyspnea on exertion and fatigue and should be worked up more broadly before attributing it to MAC. In view of this, it would not be unreasonable to follow her clinically and see her again in 6 to 8 weeks. In this context, we also should consider the untoward impact of repeated radiation exposure derived from multiple CT scans. When a patient has an abnormality on CT scan, it often leads to further scans even if the symptoms do not match the previous findings, as in this case.

►Dr. Swamy. Given her ongoing fatigue and systemic symptoms (morning stiffness of the shoulders, legs, and thighs, and leg cramps), she was referred to the rheumatology department where the physical examination revealed muscle tenderness in her proximal arms and legs with normal strength, tender points at the elbows and medial side of the bilateral knees, significant tenderness of lower legs, and no synovitis.

Dr. Monach, can you walk us through your approach to this patient? Are we seeing manifestations of fibromyalgia? What diagnoses concerns you and how would you proceed?

►Dr. Monach. The history and exam are most helpful in raising or reducing suspicion for an underlying inflammatory disease. Areas of tenderness described in her case are typical of fibromyalgia, although it can be difficult to interpret symptoms in the hip girdle and shoulder girdle because objective findings are often absent on exam in patients with inflammatory arthritis or bursitis. Similarly, tenderness at sites of tendon insertion (enthuses) without objective abnormalities is common in different forms of spondyloarthritis, so tenderness at the elbow, knee, lateral hip, and low back can be difficult to interpret. What this patient is lacking is prominent subjective or objective findings in the joints most commonly affected in rheumatoid arthritis and lupus: wrists, hands, ankles, and feet.

►Dr. Swamy. Initial laboratory data include an erythrocyte sedimentation rate of 79 with a normal C-reactive protein. A tentative diagnosis of polymyalgia rheumatic is made with consideration of a trial treatment of prednisone.

Dr. Monach, this patient has an indolent infection and is about to be given glucocorticoids. Could you describe the situations in which you feel that glucocorticoids cause a relative immunosuppression?

►Dr. Monach. Glucocorticoids are considered safe in a patient whose infection is not intrinsically dangerous or who has started appropriate antibiotics for that infection. Although all toxicities of glucocorticoids are dose dependent, the long-standing assertion that doses below 10 mg to 15 mg do not increase risk of infection is contradicted by data published in the past 10 to 15 years, with the caveat that these patients were on long-term treatment.

►Dr. Swamy. The patient was started on prednisone 15 mg per day for 15 days. She returned to the clinic after 1 week of prednisone troutment and noted “significant improvement in fatigue, morning stiffness of shoulders, thighs, leg, back is better, leg cramps resolved, shooting pain in many joints resolved.” Further laboratory results were notable for a negative rheumatoid factor, negative antinuclear antibody, and a cyclic citrullinated peptide of 60. A presumptive diagnosis of rheumatoid arthritis (RA) was made and plaquenil 200 mg twice daily was started.

Dr. Monach, can you explain why RA comes up now on serology but was not considered initially? Why does this presentation fit RA, and was her response to treatment typical? How does this fit in with her previous diagnosis of fibromyalgia? Was that just an atypical, indolent presentation of RA?

►Dr. Monach. Though her presentation is atypical for RA, in elderly patients, RA can present with symptoms resembling polymyalgia rheumatica. The question is whether she had RA all along (in which case “elderly onset” would not apply) or had fibromyalgia and developed RA more recently. The response to empiric glucocorticoid therapy is helpful, since fibromyalgia should not improve with prednisone even in a patient with RA unless treatment of RA would allow better sleep and ability to exercise. Rheumatoid arthritis typically responds very well to prednisone in the 5-mg to 15-mg range.

►Dr. Swamy. Given the new diagnosis of an inflammatory arthritis requiring immunosuppression, bronchoscopy with BAL is performed to evaluate for the presence of MAC. These cultures were positive for MAC.

Dr. Fine, does the positive BAL culture indicate an active MAC infection?

►Dr. Fine. Yes, based on these updated data, the patient has an active MAC infection. Active infection is defined as symptoms or imaging consistent with the diagnosis, supporting microbiology data (either 2 sputum or 1 BAL sample growing MAC) and the exclusion of other causes. Previously, this patient grew MAC in just one expectorated sputum; this did not meet the microbiologic criteria. Now sputum has grown in the BAL sample; along with the CT imaging, this is enough to diagnosis active MAC infection.

Treatment for MAC must consider the details of each case. First, this is not an emergency; treatment decisions should be made with the rheumatologist to consider the planned immunosuppression. For example, we must consider potential drug interactions. A specific point should be made of the use of tumor necrosis factor (TNF)-α inhibition, which data indicate can reactivate TB and may inhibit mechanisms that restrain mycobacterial disease. Serious cases of MAC infection have been reported in the literature in the setting of TNF-α inhibition.^5,6 Despite these concerns, there is not a contraindication to using these therapies from the perspective of the active MAC disease. All of these decisions will impact the need to commit the patient to MAC therapy.

►Dr. Swamy. Dr. Fine, what do you consider prior to initiating MAC therapy?

► Dr. Fine. The decision to pursue MAC therapy should not be taken lightly. Therapy often entails prolonged multidrug regimens, usually spanning more than a year, with frequent adverse effects. Outside of very specific cases, such as TNF-β inhibition, MAC is rarely a life-threatening disease, so the benefit may be limited. Treatment for MAC is certainly unlikely to be fruitful without a diligent and motivated patient able to handle the high and prolonged pill burden. Of note, it is also important to keep this patient up-to-date with influenza and pneumonia vaccination given her structural lung disease.

►Dr. Swamy. The decision is made to treat MAC with azithromycin, rifampin, and ethambutol. The disease is noted to be nonfibrocavitary. The patient underwent monthly liver function test monitoring and visual acuity testing, which were unremarkable. Dr. Fine, can you describe the phenotypes of nontuberculous mycobacterial (NTM) disease?

►Dr. Fine. There are 3 main phenotypes of NTM.³ First, we see the elderly man with preexisting lung disease—usually chronic obstructive pulmonary disease—with fibrocavitary and/or reticulonodular appearance. Second, we see the slim, elderly woman often without any preexisting lung disease presenting with focal bronchiectasis and nodular lesions in right middle lobe and lingula—the Lady Windermere syndrome. This eponym is derived from Oscar Wilde’s play “Lady Windermere’s Fan, a Play About a Good Woman,” and was first associated with this disease in 1992.⁷ At the time, it was thought that the voluntary suppression of cough led to poorly draining lung regions, vulnerable to engraftment by atypical mycobacteria. Infection with atypical mycobacteria are associated with this population; however, it is no longer thought to be due to the voluntary suppression of cough.^7,8 Third, we do occasionally see atypical presentations, such as focal masses and solitary nodules.

►Dr. Swamy. At 1-year follow-up she successfully completed MAC therapy and noted ongoing control of rheumatoid symptoms.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

The Centers for Disease Control and Prevention (CDC) is a US federal agency under the Department of Health and Human Services. It is the nation’s leading public health institute. Its main goal is to save lives and protect people from health, safety, and security threats. The CDC website lists 25 no-cost applications that the agency has developed: https://www.cdc.gov/mobile/mobileapp.html.

This review will focus on 3 CDC apps (Table) that I feel are useful to ObGyn health care providers: Prevent Group B Strep (GBS), STD Tx Guide, and US Medical Eligibility Criteria for Contraceptive Use. In fact, in an evaluation of contraception apps for providers of family planning services, US Medical Eligibility Criteria for Contraceptive Use was one of the highest scoring apps.¹ I will evaluate each app by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).² I commend the CDC for developing these useful tools to assist health care providers.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Centers for Disease Control and Prevention (CDC) is a US federal agency under the Department of Health and Human Services. It is the nation’s leading public health institute. Its main goal is to save lives and protect people from health, safety, and security threats. The CDC website lists 25 no-cost applications that the agency has developed: https://www.cdc.gov/mobile/mobileapp.html.

This review will focus on 3 CDC apps (Table) that I feel are useful to ObGyn health care providers: Prevent Group B Strep (GBS), STD Tx Guide, and US Medical Eligibility Criteria for Contraceptive Use. In fact, in an evaluation of contraception apps for providers of family planning services, US Medical Eligibility Criteria for Contraceptive Use was one of the highest scoring apps.¹ I will evaluate each app by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).² I commend the CDC for developing these useful tools to assist health care providers.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Centers for Disease Control and Prevention (CDC) is a US federal agency under the Department of Health and Human Services. It is the nation’s leading public health institute. Its main goal is to save lives and protect people from health, safety, and security threats. The CDC website lists 25 no-cost applications that the agency has developed: https://www.cdc.gov/mobile/mobileapp.html.

This review will focus on 3 CDC apps (Table) that I feel are useful to ObGyn health care providers: Prevent Group B Strep (GBS), STD Tx Guide, and US Medical Eligibility Criteria for Contraceptive Use. In fact, in an evaluation of contraception apps for providers of family planning services, US Medical Eligibility Criteria for Contraceptive Use was one of the highest scoring apps.¹ I will evaluate each app by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).² I commend the CDC for developing these useful tools to assist health care providers.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Many articles about physician burnout and more alarmingly depression and suicide include chilling statistics; however, the data are limited. The same study from Medscape about burnout broken down by medical specialty often is cited.¹ Although dermatology fares better than many specialties in this research, the percentages are still abysmal.

I am writing as a physician, for physicians. I do not want to quote the data to you. If you are reading this article, you have probably felt some burnout, even transiently. Maybe you even feel it now, at this very moment. Physicians are competitive capable people. I do not want to present numbers and statistics that make you question the validity of your feelings, whether you fit with the average statistics, or make you try to calculate how many of your friends or colleagues match these statistics. The numbers are terrible, no matter how you look at them, and all trends show them worsening with time.

What is burnout?

To simply define burnout as fatigue or high workload would be to undervalue the term. Physicians are trained through college, medical school, and countless hours of residency to cope with both challenges. Maslach et al² defined burnout as “a psychological syndrome in response to chronic interpersonal stressors on the job” leading to “overwhelming exhaustion, feelings of cynicism and detachment from the job, and a sense of ineffectiveness and lack of accomplishment.”

Who does burnout affect?

Physician burnout affects both the patient and the physician. It has been demonstrated that physician burnout leads to lower patient satisfaction and care as well as higher risk for medical errors. There are the more obvious and direct effects on the physician, with affected physicians having much higher employment turnover and risk for addiction and suicide.³ One could argue that there are even more downstream effects of burnout, including physicians’ families who may be directly affected and even societal effects when fully trained physicians leave the clinical arena to pursue other careers.

How do you recognize when you are burnt out?

The first time I recognized that I was burnt out was in medical school. I understood my burnout through the lens of my undergraduate training in anthropology as compassion fatigue, a term that has been used to describe the lack of empathy that can develop when any individual is presented with an overwhelming tragedy or horror. When you are in survival mode—waking up just to survive the next day or clinic shift or call—you are surviving but hardly thriving as a physician.³ I believe that humans have a tremendous capacity for survival, but when we are in survival mode we have little energy leftover for the pleasures of life, from family to hobbies. I would similarly argue that in survival mode we have limited ability to appreciate the pain and suffering our patients are experiencing. Survival mode limits our ability as physicians to connect with our patients and to engage in the full spectrum of emotion in our time outside of our job.

What are the causes of burnout in dermatology?

As dermatologists, we often have milder on-call schedules and fewer critically ill patients than many of our medical colleagues. For this reason, we may be afraid to address the real role of physician burnout in our field. Fellow dermatologist Jeffrey Benabio, MD (San Diego, California), notes that the phrase dermatologist burnout may even seem oxymoronic, but we face many of the same daily frustrations with electronic medical records, increasing patient volume, and insurance struggles.⁴ The electronic medical record looms large in many physicians’ complaints these days. A recent article in the New York Times described the physician as “the highest-paid clerical worker in the hospital,”⁵ which is not wrong. For every hour of patient time, we have nearly double that spent on paperwork.⁵

Dike Drummond, MD, a family practice physician who focuses on physician burnout, notes that physicians are taught very early to put the patient first, but it is never discussed when or how to turn this switch off.³ However, there is little written about dermatology-specific burnout. A problem that is not studied or even considered will be harder to fix.

Why does it matter?

I believe that addressing physician burnout is critical for 2 reasons: (1) we can improve patient care by improving patient satisfaction and decreasing medical error, and (2) we can find greater satisfaction and professional fulfillment while caring for our patients. Ultimately, patient care and physician care are intimately linked; as stated by Thomas et al,⁶ “[p]hysicians who are well can best serve their patients.”

As a resident in 2018, I recognize that my coresidents and I are training as physicians in the time of “duty hours” and an ongoing discussion of burnout. However, I sense a burnout fatigue setting in among residents, many who do not want to discuss wellness anymore. The newer data suggest that work hour restrictions do not improve patient safety, negating one of the driving reasons for the change.⁷ At the same time, residency programs are initiating wellness programs in response to the growing literature on physician burnout. These wellness programs vary in the types of activities included, from individual coping techniques such as mindfulness training to social gatherings for the residents. In general, these wellness initiatives focus on burnout at the individual level, but they do not take into account systemic or structural challenges that might contribute to this worsening epidemic.

Final Thoughts

As a profession, I believe that physicians have internalized the concept of burnout to equate with a personal individual failing. At various times in my training, I have felt that if I could just practice mediation, study more, or shift my perspective, I personally could overcome burnout. I have intermittently felt my burnout as proof that I should never have become a physician. As a woman and the first physician in my family, fighting the sense of burnout so early in my career seemed demoralizing and nearly drove me to change my career path. It exacerbated my sense of imposter syndrome: that I never truly belonged in medicine at all. After much soul-searching, I have concluded that burnout is a concept propagated by administrators and businesspeople to stigmatize the reaction by many physicians to the growing trends in medicine and cast it as a personal failure rather than as the symptom of a broken medical system.

If we continue to identify burnout as an individual failing and treat it as such, I believe that we will fail to stem the growing trend within dermatology and within medicine more broadly. We need to consider the driving factors behind dermatology burnout so that we can begin to address them at a structural level.

Many articles about physician burnout and more alarmingly depression and suicide include chilling statistics; however, the data are limited. The same study from Medscape about burnout broken down by medical specialty often is cited.¹ Although dermatology fares better than many specialties in this research, the percentages are still abysmal.

I am writing as a physician, for physicians. I do not want to quote the data to you. If you are reading this article, you have probably felt some burnout, even transiently. Maybe you even feel it now, at this very moment. Physicians are competitive capable people. I do not want to present numbers and statistics that make you question the validity of your feelings, whether you fit with the average statistics, or make you try to calculate how many of your friends or colleagues match these statistics. The numbers are terrible, no matter how you look at them, and all trends show them worsening with time.

What is burnout?

To simply define burnout as fatigue or high workload would be to undervalue the term. Physicians are trained through college, medical school, and countless hours of residency to cope with both challenges. Maslach et al² defined burnout as “a psychological syndrome in response to chronic interpersonal stressors on the job” leading to “overwhelming exhaustion, feelings of cynicism and detachment from the job, and a sense of ineffectiveness and lack of accomplishment.”

Who does burnout affect?

Physician burnout affects both the patient and the physician. It has been demonstrated that physician burnout leads to lower patient satisfaction and care as well as higher risk for medical errors. There are the more obvious and direct effects on the physician, with affected physicians having much higher employment turnover and risk for addiction and suicide.³ One could argue that there are even more downstream effects of burnout, including physicians’ families who may be directly affected and even societal effects when fully trained physicians leave the clinical arena to pursue other careers.

How do you recognize when you are burnt out?

The first time I recognized that I was burnt out was in medical school. I understood my burnout through the lens of my undergraduate training in anthropology as compassion fatigue, a term that has been used to describe the lack of empathy that can develop when any individual is presented with an overwhelming tragedy or horror. When you are in survival mode—waking up just to survive the next day or clinic shift or call—you are surviving but hardly thriving as a physician.³ I believe that humans have a tremendous capacity for survival, but when we are in survival mode we have little energy leftover for the pleasures of life, from family to hobbies. I would similarly argue that in survival mode we have limited ability to appreciate the pain and suffering our patients are experiencing. Survival mode limits our ability as physicians to connect with our patients and to engage in the full spectrum of emotion in our time outside of our job.

What are the causes of burnout in dermatology?

As dermatologists, we often have milder on-call schedules and fewer critically ill patients than many of our medical colleagues. For this reason, we may be afraid to address the real role of physician burnout in our field. Fellow dermatologist Jeffrey Benabio, MD (San Diego, California), notes that the phrase dermatologist burnout may even seem oxymoronic, but we face many of the same daily frustrations with electronic medical records, increasing patient volume, and insurance struggles.⁴ The electronic medical record looms large in many physicians’ complaints these days. A recent article in the New York Times described the physician as “the highest-paid clerical worker in the hospital,”⁵ which is not wrong. For every hour of patient time, we have nearly double that spent on paperwork.⁵

Dike Drummond, MD, a family practice physician who focuses on physician burnout, notes that physicians are taught very early to put the patient first, but it is never discussed when or how to turn this switch off.³ However, there is little written about dermatology-specific burnout. A problem that is not studied or even considered will be harder to fix.

Why does it matter?

I believe that addressing physician burnout is critical for 2 reasons: (1) we can improve patient care by improving patient satisfaction and decreasing medical error, and (2) we can find greater satisfaction and professional fulfillment while caring for our patients. Ultimately, patient care and physician care are intimately linked; as stated by Thomas et al,⁶ “[p]hysicians who are well can best serve their patients.”

As a resident in 2018, I recognize that my coresidents and I are training as physicians in the time of “duty hours” and an ongoing discussion of burnout. However, I sense a burnout fatigue setting in among residents, many who do not want to discuss wellness anymore. The newer data suggest that work hour restrictions do not improve patient safety, negating one of the driving reasons for the change.⁷ At the same time, residency programs are initiating wellness programs in response to the growing literature on physician burnout. These wellness programs vary in the types of activities included, from individual coping techniques such as mindfulness training to social gatherings for the residents. In general, these wellness initiatives focus on burnout at the individual level, but they do not take into account systemic or structural challenges that might contribute to this worsening epidemic.

Final Thoughts

As a profession, I believe that physicians have internalized the concept of burnout to equate with a personal individual failing. At various times in my training, I have felt that if I could just practice mediation, study more, or shift my perspective, I personally could overcome burnout. I have intermittently felt my burnout as proof that I should never have become a physician. As a woman and the first physician in my family, fighting the sense of burnout so early in my career seemed demoralizing and nearly drove me to change my career path. It exacerbated my sense of imposter syndrome: that I never truly belonged in medicine at all. After much soul-searching, I have concluded that burnout is a concept propagated by administrators and businesspeople to stigmatize the reaction by many physicians to the growing trends in medicine and cast it as a personal failure rather than as the symptom of a broken medical system.

If we continue to identify burnout as an individual failing and treat it as such, I believe that we will fail to stem the growing trend within dermatology and within medicine more broadly. We need to consider the driving factors behind dermatology burnout so that we can begin to address them at a structural level.

Many articles about physician burnout and more alarmingly depression and suicide include chilling statistics; however, the data are limited. The same study from Medscape about burnout broken down by medical specialty often is cited.¹ Although dermatology fares better than many specialties in this research, the percentages are still abysmal.

I am writing as a physician, for physicians. I do not want to quote the data to you. If you are reading this article, you have probably felt some burnout, even transiently. Maybe you even feel it now, at this very moment. Physicians are competitive capable people. I do not want to present numbers and statistics that make you question the validity of your feelings, whether you fit with the average statistics, or make you try to calculate how many of your friends or colleagues match these statistics. The numbers are terrible, no matter how you look at them, and all trends show them worsening with time.

What is burnout?

To simply define burnout as fatigue or high workload would be to undervalue the term. Physicians are trained through college, medical school, and countless hours of residency to cope with both challenges. Maslach et al² defined burnout as “a psychological syndrome in response to chronic interpersonal stressors on the job” leading to “overwhelming exhaustion, feelings of cynicism and detachment from the job, and a sense of ineffectiveness and lack of accomplishment.”

Who does burnout affect?

Physician burnout affects both the patient and the physician. It has been demonstrated that physician burnout leads to lower patient satisfaction and care as well as higher risk for medical errors. There are the more obvious and direct effects on the physician, with affected physicians having much higher employment turnover and risk for addiction and suicide.³ One could argue that there are even more downstream effects of burnout, including physicians’ families who may be directly affected and even societal effects when fully trained physicians leave the clinical arena to pursue other careers.

How do you recognize when you are burnt out?

The first time I recognized that I was burnt out was in medical school. I understood my burnout through the lens of my undergraduate training in anthropology as compassion fatigue, a term that has been used to describe the lack of empathy that can develop when any individual is presented with an overwhelming tragedy or horror. When you are in survival mode—waking up just to survive the next day or clinic shift or call—you are surviving but hardly thriving as a physician.³ I believe that humans have a tremendous capacity for survival, but when we are in survival mode we have little energy leftover for the pleasures of life, from family to hobbies. I would similarly argue that in survival mode we have limited ability to appreciate the pain and suffering our patients are experiencing. Survival mode limits our ability as physicians to connect with our patients and to engage in the full spectrum of emotion in our time outside of our job.

What are the causes of burnout in dermatology?

As dermatologists, we often have milder on-call schedules and fewer critically ill patients than many of our medical colleagues. For this reason, we may be afraid to address the real role of physician burnout in our field. Fellow dermatologist Jeffrey Benabio, MD (San Diego, California), notes that the phrase dermatologist burnout may even seem oxymoronic, but we face many of the same daily frustrations with electronic medical records, increasing patient volume, and insurance struggles.⁴ The electronic medical record looms large in many physicians’ complaints these days. A recent article in the New York Times described the physician as “the highest-paid clerical worker in the hospital,”⁵ which is not wrong. For every hour of patient time, we have nearly double that spent on paperwork.⁵

Dike Drummond, MD, a family practice physician who focuses on physician burnout, notes that physicians are taught very early to put the patient first, but it is never discussed when or how to turn this switch off.³ However, there is little written about dermatology-specific burnout. A problem that is not studied or even considered will be harder to fix.

Why does it matter?

I believe that addressing physician burnout is critical for 2 reasons: (1) we can improve patient care by improving patient satisfaction and decreasing medical error, and (2) we can find greater satisfaction and professional fulfillment while caring for our patients. Ultimately, patient care and physician care are intimately linked; as stated by Thomas et al,⁶ “[p]hysicians who are well can best serve their patients.”

As a resident in 2018, I recognize that my coresidents and I are training as physicians in the time of “duty hours” and an ongoing discussion of burnout. However, I sense a burnout fatigue setting in among residents, many who do not want to discuss wellness anymore. The newer data suggest that work hour restrictions do not improve patient safety, negating one of the driving reasons for the change.⁷ At the same time, residency programs are initiating wellness programs in response to the growing literature on physician burnout. These wellness programs vary in the types of activities included, from individual coping techniques such as mindfulness training to social gatherings for the residents. In general, these wellness initiatives focus on burnout at the individual level, but they do not take into account systemic or structural challenges that might contribute to this worsening epidemic.

Final Thoughts

As a profession, I believe that physicians have internalized the concept of burnout to equate with a personal individual failing. At various times in my training, I have felt that if I could just practice mediation, study more, or shift my perspective, I personally could overcome burnout. I have intermittently felt my burnout as proof that I should never have become a physician. As a woman and the first physician in my family, fighting the sense of burnout so early in my career seemed demoralizing and nearly drove me to change my career path. It exacerbated my sense of imposter syndrome: that I never truly belonged in medicine at all. After much soul-searching, I have concluded that burnout is a concept propagated by administrators and businesspeople to stigmatize the reaction by many physicians to the growing trends in medicine and cast it as a personal failure rather than as the symptom of a broken medical system.

If we continue to identify burnout as an individual failing and treat it as such, I believe that we will fail to stem the growing trend within dermatology and within medicine more broadly. We need to consider the driving factors behind dermatology burnout so that we can begin to address them at a structural level.

The facts

Title X, a bill originally passed in 1970 under President Nixon, is the only federal grant program dedicated to providing family planning services as well as other preventive health care to primarily low-income patients. It is estimated that 70% of patients using Title X services are below the federal poverty level and more than 60% are uninsured or underinsured.¹

In 2015 alone, Title X clinics served 3.8 million women, preventing 822,300 unintended pregnancies and 277,800 abortions.² These clinics provide comprehensive family planning services including information, counseling, and referrals for abortion services. Title X clinics do not use the funding to provide abortion care, and no federal funding from Title X has ever been used to pay for abortions.

Proposed rule changes

The Trump Administration has proposed several new rules for Title X grant recipients.

Here are the main changes³:

• There must be a “financial and physical” separation between a clinic that is a Title X grant recipient and a facility where “abortion is a method of family planning.” This would prevent health centers that receive Title X funding from providing abortions at the same facility. This rule would predominantly affect health centers like Planned Parenthood. Although these clinics already have a financial separation from abortion care, there would not be a physical one in most situations and these clinics would lose Title X funding or be forced to stop providing abortion services.
• Providers who work at a clinic that receives Title X funding but provides abortions at a completely different facility may be ineligible for ongoing Title X grant money. In the new changes, “funds may not be used…to support the separate abortion business of Title X grant subrecipient.” The changes also propose to “protect Title X providers” from choosing between the health of their patients and their consciences. It plans to do this by removing the requirement to provide abortion counseling and referral and allows “non-directive” counseling.
• There would also be a requirement to encourage more parental involvement in minors’ decision making. While clinics already discuss parental involvement, the change would seek to increase the encouragement to young patients to involve parents. Most young patients do involve a parent or guardian in their care; however, many Title X clinics serve young patients who seek care confidentially. Patients seek confidential care due to a multitude of reasons, including history of abuse, lack of trust, and intimate partner violence.
• “A Title X project may not perform, promote, refer for, or support abortion as a method of family planning.” Although the rule does not prevent providers from discussing abortions, clinicians could offer little guidance if a patient opts for an abortion. Providers can give a list of “qualified, comprehensive health service providers” but may not disclose which, if any, of the providers perform abortions.

Take action

Title X provides important health care services to low-income, uninsured, and underinsured patients. These proposals put access to comprehensive health care for vulnerable populations at risk. Medical organizations including the American Medical Association and American College of Obstetricians and Gynecologists have made statements against the proposed changes to Title X. As ObGyns, we need to ensure our patients are fully informed and have access to all family planning and preventive health services.

Call or email your local representative and tell them you oppose the changes to Title X. Find your representatives here.

Follow ACOG’s Action Center on protecting Title X, which includes a flyer for your waiting room.

Send a message to the Health and Human Services Secretary. Submit a formal comment through July 31, 2018, on the Federal Registrar website expressing your thoughts with these proposed changes.

The facts

Title X, a bill originally passed in 1970 under President Nixon, is the only federal grant program dedicated to providing family planning services as well as other preventive health care to primarily low-income patients. It is estimated that 70% of patients using Title X services are below the federal poverty level and more than 60% are uninsured or underinsured.¹

In 2015 alone, Title X clinics served 3.8 million women, preventing 822,300 unintended pregnancies and 277,800 abortions.² These clinics provide comprehensive family planning services including information, counseling, and referrals for abortion services. Title X clinics do not use the funding to provide abortion care, and no federal funding from Title X has ever been used to pay for abortions.

Proposed rule changes

The Trump Administration has proposed several new rules for Title X grant recipients.

Here are the main changes³:

• There must be a “financial and physical” separation between a clinic that is a Title X grant recipient and a facility where “abortion is a method of family planning.” This would prevent health centers that receive Title X funding from providing abortions at the same facility. This rule would predominantly affect health centers like Planned Parenthood. Although these clinics already have a financial separation from abortion care, there would not be a physical one in most situations and these clinics would lose Title X funding or be forced to stop providing abortion services.
• Providers who work at a clinic that receives Title X funding but provides abortions at a completely different facility may be ineligible for ongoing Title X grant money. In the new changes, “funds may not be used…to support the separate abortion business of Title X grant subrecipient.” The changes also propose to “protect Title X providers” from choosing between the health of their patients and their consciences. It plans to do this by removing the requirement to provide abortion counseling and referral and allows “non-directive” counseling.
• There would also be a requirement to encourage more parental involvement in minors’ decision making. While clinics already discuss parental involvement, the change would seek to increase the encouragement to young patients to involve parents. Most young patients do involve a parent or guardian in their care; however, many Title X clinics serve young patients who seek care confidentially. Patients seek confidential care due to a multitude of reasons, including history of abuse, lack of trust, and intimate partner violence.
• “A Title X project may not perform, promote, refer for, or support abortion as a method of family planning.” Although the rule does not prevent providers from discussing abortions, clinicians could offer little guidance if a patient opts for an abortion. Providers can give a list of “qualified, comprehensive health service providers” but may not disclose which, if any, of the providers perform abortions.

Take action

Title X provides important health care services to low-income, uninsured, and underinsured patients. These proposals put access to comprehensive health care for vulnerable populations at risk. Medical organizations including the American Medical Association and American College of Obstetricians and Gynecologists have made statements against the proposed changes to Title X. As ObGyns, we need to ensure our patients are fully informed and have access to all family planning and preventive health services.

Call or email your local representative and tell them you oppose the changes to Title X. Find your representatives here.

Follow ACOG’s Action Center on protecting Title X, which includes a flyer for your waiting room.

Send a message to the Health and Human Services Secretary. Submit a formal comment through July 31, 2018, on the Federal Registrar website expressing your thoughts with these proposed changes.

The facts

Title X, a bill originally passed in 1970 under President Nixon, is the only federal grant program dedicated to providing family planning services as well as other preventive health care to primarily low-income patients. It is estimated that 70% of patients using Title X services are below the federal poverty level and more than 60% are uninsured or underinsured.¹

In 2015 alone, Title X clinics served 3.8 million women, preventing 822,300 unintended pregnancies and 277,800 abortions.² These clinics provide comprehensive family planning services including information, counseling, and referrals for abortion services. Title X clinics do not use the funding to provide abortion care, and no federal funding from Title X has ever been used to pay for abortions.

Proposed rule changes

The Trump Administration has proposed several new rules for Title X grant recipients.

Here are the main changes³:

• There must be a “financial and physical” separation between a clinic that is a Title X grant recipient and a facility where “abortion is a method of family planning.” This would prevent health centers that receive Title X funding from providing abortions at the same facility. This rule would predominantly affect health centers like Planned Parenthood. Although these clinics already have a financial separation from abortion care, there would not be a physical one in most situations and these clinics would lose Title X funding or be forced to stop providing abortion services.
• Providers who work at a clinic that receives Title X funding but provides abortions at a completely different facility may be ineligible for ongoing Title X grant money. In the new changes, “funds may not be used…to support the separate abortion business of Title X grant subrecipient.” The changes also propose to “protect Title X providers” from choosing between the health of their patients and their consciences. It plans to do this by removing the requirement to provide abortion counseling and referral and allows “non-directive” counseling.
• There would also be a requirement to encourage more parental involvement in minors’ decision making. While clinics already discuss parental involvement, the change would seek to increase the encouragement to young patients to involve parents. Most young patients do involve a parent or guardian in their care; however, many Title X clinics serve young patients who seek care confidentially. Patients seek confidential care due to a multitude of reasons, including history of abuse, lack of trust, and intimate partner violence.
• “A Title X project may not perform, promote, refer for, or support abortion as a method of family planning.” Although the rule does not prevent providers from discussing abortions, clinicians could offer little guidance if a patient opts for an abortion. Providers can give a list of “qualified, comprehensive health service providers” but may not disclose which, if any, of the providers perform abortions.

Take action

Title X provides important health care services to low-income, uninsured, and underinsured patients. These proposals put access to comprehensive health care for vulnerable populations at risk. Medical organizations including the American Medical Association and American College of Obstetricians and Gynecologists have made statements against the proposed changes to Title X. As ObGyns, we need to ensure our patients are fully informed and have access to all family planning and preventive health services.

Call or email your local representative and tell them you oppose the changes to Title X. Find your representatives here.

Follow ACOG’s Action Center on protecting Title X, which includes a flyer for your waiting room.

Send a message to the Health and Human Services Secretary. Submit a formal comment through July 31, 2018, on the Federal Registrar website expressing your thoughts with these proposed changes.

I’m in really good shape. Well, more like really not bad shape. I eat healthy food (see my previous column on diet) and work out nearly every day. I have done so for years. I’ve learned that working out doesn’t make much difference with my weight, but it makes a huge difference with my mood, even more so than meditating. That’s why I’ll never give it up.

My approach is to vary my routine, typically by month. I’ve done “BUD/S qualification” months where I do only push-ups, sit-ups, pull-ups, and runs to meet the minimum requirements for the Navy Seal Training. (It’s not as hard as you might think, although I’m pretty lenient on form.)

When I have an hour to exercise and I’m deep into a podcast, then I’ll just keep going. If I’m trying to work out a piece I’m writing, like this one, then I’ll go for a run along the harbor here in San Diego. If I have to catch an early flight or drive to LA for the day, then I might have only 15 minutes. In that instance, I do high-intensity sprints, also known as high-intensity interval training (HIIT). Although it’s hard to break a good sweat, these workouts are both challenging and rewarding.

Recently, I participated in a wonderful physician wellness program at Kaiser Permanente, San Diego, where, over several weeks, we learned about nutrition, practiced meditation, and did Tabatas. What’s a Tabata you ask? It’s a kick in the butt.

Tabata training is a type of HIIT training. Whereas HIIT workouts range from 15 to 45 minutes, Tabata workouts last 4 minutes. Yup, it’s a 4-minute workout that consists of 20 seconds of all-out, maximum effort, followed by 10 seconds of rest. The specific move you do for Tabatas is up to you, but it’s recommended that it be the same move for all 4 minutes. I like burpees which work your entire body – you jump, you drop into a push-up position, you pull your feet back in, and jump again. (Check out a video on YouTube.)

When we started the class, I thought Tabatas would be too easy for a gym rat like me. Plus, there were pediatricians, and even radiologists there, so how hard could they be? Let’s just say I couldn’t sit for 2 days after my first session: That’s how hard.

Tabatas are also a quick way to torch calories. A study published in the Journal of Sports Science and Medicine in 2013 found subjects who performed a 20-minute Tabata session experienced improved cardiorespiratory endurance and increased calorie burn (J Sports Sci Med. 2013 Sep;12[3]: 612-3).

Sometimes on a Monday, which is typically my difficult day, I’ll break out a few burpees in my office between patients. The energy jolt is real, and unlike caffeine, doesn’t leave me shaky. Because Tabatas require physical and mental focus, they’re an effective way to clear your mind after a grueling patient visit or if you’re feeling distracted. You simply can’t be thinking about that late patient or angry email when you’re jumping and lunging at full speed.

All the physicians in our program liked the Tabatas; many were even better than me. (Turns out we have pediatricians and radiologists who do things like run the Boston marathon and win Spartan races).

And if you start doing Tabatas, feel free to email me if you need a recommendation for a standing desk – you might not be able to sit as much afterward.


 

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 in really good shape. Well, more like really not bad shape. I eat healthy food (see my previous column on diet) and work out nearly every day. I have done so for years. I’ve learned that working out doesn’t make much difference with my weight, but it makes a huge difference with my mood, even more so than meditating. That’s why I’ll never give it up.

My approach is to vary my routine, typically by month. I’ve done “BUD/S qualification” months where I do only push-ups, sit-ups, pull-ups, and runs to meet the minimum requirements for the Navy Seal Training. (It’s not as hard as you might think, although I’m pretty lenient on form.)

When I have an hour to exercise and I’m deep into a podcast, then I’ll just keep going. If I’m trying to work out a piece I’m writing, like this one, then I’ll go for a run along the harbor here in San Diego. If I have to catch an early flight or drive to LA for the day, then I might have only 15 minutes. In that instance, I do high-intensity sprints, also known as high-intensity interval training (HIIT). Although it’s hard to break a good sweat, these workouts are both challenging and rewarding.

Recently, I participated in a wonderful physician wellness program at Kaiser Permanente, San Diego, where, over several weeks, we learned about nutrition, practiced meditation, and did Tabatas. What’s a Tabata you ask? It’s a kick in the butt.

Tabata training is a type of HIIT training. Whereas HIIT workouts range from 15 to 45 minutes, Tabata workouts last 4 minutes. Yup, it’s a 4-minute workout that consists of 20 seconds of all-out, maximum effort, followed by 10 seconds of rest. The specific move you do for Tabatas is up to you, but it’s recommended that it be the same move for all 4 minutes. I like burpees which work your entire body – you jump, you drop into a push-up position, you pull your feet back in, and jump again. (Check out a video on YouTube.)

When we started the class, I thought Tabatas would be too easy for a gym rat like me. Plus, there were pediatricians, and even radiologists there, so how hard could they be? Let’s just say I couldn’t sit for 2 days after my first session: That’s how hard.

Tabatas are also a quick way to torch calories. A study published in the Journal of Sports Science and Medicine in 2013 found subjects who performed a 20-minute Tabata session experienced improved cardiorespiratory endurance and increased calorie burn (J Sports Sci Med. 2013 Sep;12[3]: 612-3).

Sometimes on a Monday, which is typically my difficult day, I’ll break out a few burpees in my office between patients. The energy jolt is real, and unlike caffeine, doesn’t leave me shaky. Because Tabatas require physical and mental focus, they’re an effective way to clear your mind after a grueling patient visit or if you’re feeling distracted. You simply can’t be thinking about that late patient or angry email when you’re jumping and lunging at full speed.

All the physicians in our program liked the Tabatas; many were even better than me. (Turns out we have pediatricians and radiologists who do things like run the Boston marathon and win Spartan races).

And if you start doing Tabatas, feel free to email me if you need a recommendation for a standing desk – you might not be able to sit as much afterward.


 

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 in really good shape. Well, more like really not bad shape. I eat healthy food (see my previous column on diet) and work out nearly every day. I have done so for years. I’ve learned that working out doesn’t make much difference with my weight, but it makes a huge difference with my mood, even more so than meditating. That’s why I’ll never give it up.

My approach is to vary my routine, typically by month. I’ve done “BUD/S qualification” months where I do only push-ups, sit-ups, pull-ups, and runs to meet the minimum requirements for the Navy Seal Training. (It’s not as hard as you might think, although I’m pretty lenient on form.)

When I have an hour to exercise and I’m deep into a podcast, then I’ll just keep going. If I’m trying to work out a piece I’m writing, like this one, then I’ll go for a run along the harbor here in San Diego. If I have to catch an early flight or drive to LA for the day, then I might have only 15 minutes. In that instance, I do high-intensity sprints, also known as high-intensity interval training (HIIT). Although it’s hard to break a good sweat, these workouts are both challenging and rewarding.

Recently, I participated in a wonderful physician wellness program at Kaiser Permanente, San Diego, where, over several weeks, we learned about nutrition, practiced meditation, and did Tabatas. What’s a Tabata you ask? It’s a kick in the butt.

Tabata training is a type of HIIT training. Whereas HIIT workouts range from 15 to 45 minutes, Tabata workouts last 4 minutes. Yup, it’s a 4-minute workout that consists of 20 seconds of all-out, maximum effort, followed by 10 seconds of rest. The specific move you do for Tabatas is up to you, but it’s recommended that it be the same move for all 4 minutes. I like burpees which work your entire body – you jump, you drop into a push-up position, you pull your feet back in, and jump again. (Check out a video on YouTube.)

When we started the class, I thought Tabatas would be too easy for a gym rat like me. Plus, there were pediatricians, and even radiologists there, so how hard could they be? Let’s just say I couldn’t sit for 2 days after my first session: That’s how hard.

Tabatas are also a quick way to torch calories. A study published in the Journal of Sports Science and Medicine in 2013 found subjects who performed a 20-minute Tabata session experienced improved cardiorespiratory endurance and increased calorie burn (J Sports Sci Med. 2013 Sep;12[3]: 612-3).

Sometimes on a Monday, which is typically my difficult day, I’ll break out a few burpees in my office between patients. The energy jolt is real, and unlike caffeine, doesn’t leave me shaky. Because Tabatas require physical and mental focus, they’re an effective way to clear your mind after a grueling patient visit or if you’re feeling distracted. You simply can’t be thinking about that late patient or angry email when you’re jumping and lunging at full speed.

All the physicians in our program liked the Tabatas; many were even better than me. (Turns out we have pediatricians and radiologists who do things like run the Boston marathon and win Spartan races).

And if you start doing Tabatas, feel free to email me if you need a recommendation for a standing desk – you might not be able to sit as much afterward.


 

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].

Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.

The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.

Case Presentation

A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.

The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.

The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.

The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.

She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.

She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.

The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.

After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.

Treatment Outcomes

The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2

After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.

Discussion

The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.^3,4

Terminology

Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.^1,2

Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.

Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender. 

Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.

Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.

Improving Patient Interaction

Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.

The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.¹ The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.

Medical Treatment

Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy^..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.^1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.^1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.

The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.² However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.

The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.¹

Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy. 

For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal. 

Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.² The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.² 

Physical Changes With Hormone Therapy

Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.²

Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.² Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.

Routine Health Maintenance

Breast Cancer Screening

Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.² Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.⁶

Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.

Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.^2,7-10

A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.⁸ A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.⁹ A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.¹⁰

In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.¹¹

Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.² For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.

Prostate Cancer Screening

Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.^12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.¹

Cervical Cancer Screening

When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.

Hematology Health

Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.^14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).¹ All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.¹ The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.^14-16

Sexual Health

Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.¹⁷ Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.

Cardiovascular Health

The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.^18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.^1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.

As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.^18,19

Conclusion

In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.

Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.

Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.

The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.

Case Presentation

A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.

The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.

The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.

The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.

She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.

She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.

The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.

After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.

Treatment Outcomes

The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2

After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.

Discussion

The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.^3,4

Terminology

Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.^1,2

Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.

Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender. 

Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.

Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.

Improving Patient Interaction

Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.

The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.¹ The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.

Medical Treatment

Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy^..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.^1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.^1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.

The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.² However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.

The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.¹

Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy. 

For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal. 

Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.² The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.² 

Physical Changes With Hormone Therapy

Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.²

Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.² Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.

Routine Health Maintenance

Breast Cancer Screening

Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.² Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.⁶

Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.

Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.^2,7-10

A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.⁸ A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.⁹ A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.¹⁰

In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.¹¹

Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.² For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.

Prostate Cancer Screening

Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.^12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.¹

Cervical Cancer Screening

When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.

Hematology Health

Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.^14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).¹ All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.¹ The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.^14-16

Sexual Health

Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.¹⁷ Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.

Cardiovascular Health

The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.^18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.^1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.

As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.^18,19

Conclusion

In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.

Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.

Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.

The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.

Case Presentation

A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.

The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.

The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.

The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.

She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.

She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.

The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.

After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.

Treatment Outcomes

The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2

After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.

Discussion

The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.^3,4

Terminology

Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.^1,2

Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.

Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender. 

Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.

Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.

Improving Patient Interaction

Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.

The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.¹ The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.

Medical Treatment

Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy^..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.^1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.^1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.

The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.² However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.

The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.¹

Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy. 

For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal. 

Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.² The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.² 

Physical Changes With Hormone Therapy

Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.²

Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.² Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.

Routine Health Maintenance

Breast Cancer Screening

Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.² Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.⁶

Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.

Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.^2,7-10

A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.⁸ A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.⁹ A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.¹⁰

In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.¹¹

Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.² For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.

Prostate Cancer Screening

Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.^12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.¹

Cervical Cancer Screening

When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.

Hematology Health

Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.^14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).¹ All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.¹ The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.^14-16

Sexual Health

Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.¹⁷ Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.

Cardiovascular Health

The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.^18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.^1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.

As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.^18,19

Conclusion

In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.

Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.

Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

On Friday, June 29, at 5:42 a.m., I stood with my family on a Florida shore overlooking Kennedy Space Center. We had gathered with about a hundred other people to watch a rocket launch and were overwhelmed with excitement as the coastline erupted in fire, and the spacecraft lifted off toward the heavens. Standing there watching the spectacle, I couldn’t help but be caught up in the irony of the moment. Here we were, at the place where NASA sent the first Americans into space – on the very shores where the Apollo astronauts set off for the moon to plant our nation’s flag in the lunar dust in July of 1969. Yet now, almost 50 years later, this launch was profoundly different. The rocket wasn’t built by NASA, and the intention of its builders wasn’t exploration. This was a Falcon 9, built by SpaceX, a for-profit company founded by an enterprising billionaire. Most surprisingly, this relatively routine launch was intended to accomplish something that NASA – the United States’ own space agency – currently can’t do on its own: Launch rockets.

Since retiring the Space Shuttle in 2011, the United States has had to rely on others – including even Roscosmos (the Russian space agency) – to ferry passengers, satellites, and cargo into space. Seeing this opportunity in a multibillion-dollar industry, private enterprise has risen to the challenge, innovating more quickly and at a lower cost than “the establishment” has ever been capable of. As a result, space travel has been disrupted by corporations competing in a new “space race.” Instead of national pride or scientific dominance, this race has been fueled by profit and is quite similar to one being run in another industry: health care.

Just 1 day prior to watching the launch – on June 28 – we learned that Amazon had purchased PillPack, a prescription drug home delivery service. The stock market responded to the news, and the establishment (in this case CVS, Walgreen’s, and WalMart, among others) collectively lost $17.5 billion in one day. This isn’t the first time Amazon has disrupted the health care world; in January of this year, they, along with Berkshire Hathaway and JPMorgan Chase, announced a health care partnership to cut costs and improve care delivery for their employees. This move also sent shivers through the market, as health insurers and providers such as Aetna and United Health lost big on expectations that Amazon et al. wouldn’t stop with their own employees. Those of us watching this play out from the sidelines realized we were witnessing a revolution that would mean the end of health care delivery as we know it – and that’s not necessarily a bad thing, especially in the world of Electronic Health Records.

As you’ve probably noticed, it is quite rare to find physicians nowadays who love computers. Once an exciting novelty in health care, PCs have become a burdensome necessity and providers often feel enslaved to the EHRs that run on them. There are numerous reasons for this, but one primary cause is that the hundreds of disparate EHRs currently available sprouted out of health care – a centuries-old and very provincial industry – prior to the development of technical and regulatory standards to govern them. As they’ve grown larger and larger from their primitive underpinnings, these EHRs have become more cumbersome to navigate, and vendors have simply “bolted-on” additional features without significant changes to their near-obsolete software architecture.

It’s worth noting that a few EHR companies purport to be true innovators in platform usability, such as industry giant, Epic. According to CEO Judy Faulkner, Epic pours 50% of their revenue back into research and development (though, as Epic is a privately held company, this number can’t be verified). If accurate, Epic is truly an exception, as most electronic record companies spend about 10%-30% on improving their products – far less than they spend on recruiting new customers. Regardless, the outcome is this: Physician expectations for user interface and user experience have far outpaced the current state of the art of EHRs, and this has left a gap that new players outside the health care establishment are apt to fill.

Like Amazon, other software giants have made significant investments in health care over the past several years. According to their website, Apple has been working with hospitals, scientists, and developers to “help health care providers streamline their work, deliver better care, and conduct medical research.” Similarly, Google claims to be “making a number of big bets in health care and life sciences,” by leveraging their artificial intelligence technology to assist in clinical diagnosis and scientific discovery. In spite of a few false starts in the past, these companies are poised to do more than simply disrupt health care. As experts in user interface and design, they could truly change the way physicians interact with health care technology, and it seems like it’s no longer a question of if, but when we’ll see that happen.

The effort of SpaceX and others to change the way we launch rockets tells a story that transcends space travel – It’s a story of how new thinking, more efficient processes, and better design can disrupt the establishment. It’s worth pointing out that NASA hasn’t given up – they are continuing to develop the Space Launch System, which, when completed, will be the most powerful rocket in the world and be capable of carrying astronauts into deep space. In the meantime, however, NASA is embracing the efforts of private industry to help pave a better way forward and make space travel safer and more accessible for everyone. We are hopeful that EHR vendors and other establishment health care institutions are taking note, adapting to meet the needs of the current generation of physicians and patients, and innovating a better way to launch health care into the future.


 

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

On Friday, June 29, at 5:42 a.m., I stood with my family on a Florida shore overlooking Kennedy Space Center. We had gathered with about a hundred other people to watch a rocket launch and were overwhelmed with excitement as the coastline erupted in fire, and the spacecraft lifted off toward the heavens. Standing there watching the spectacle, I couldn’t help but be caught up in the irony of the moment. Here we were, at the place where NASA sent the first Americans into space – on the very shores where the Apollo astronauts set off for the moon to plant our nation’s flag in the lunar dust in July of 1969. Yet now, almost 50 years later, this launch was profoundly different. The rocket wasn’t built by NASA, and the intention of its builders wasn’t exploration. This was a Falcon 9, built by SpaceX, a for-profit company founded by an enterprising billionaire. Most surprisingly, this relatively routine launch was intended to accomplish something that NASA – the United States’ own space agency – currently can’t do on its own: Launch rockets.

Since retiring the Space Shuttle in 2011, the United States has had to rely on others – including even Roscosmos (the Russian space agency) – to ferry passengers, satellites, and cargo into space. Seeing this opportunity in a multibillion-dollar industry, private enterprise has risen to the challenge, innovating more quickly and at a lower cost than “the establishment” has ever been capable of. As a result, space travel has been disrupted by corporations competing in a new “space race.” Instead of national pride or scientific dominance, this race has been fueled by profit and is quite similar to one being run in another industry: health care.

Just 1 day prior to watching the launch – on June 28 – we learned that Amazon had purchased PillPack, a prescription drug home delivery service. The stock market responded to the news, and the establishment (in this case CVS, Walgreen’s, and WalMart, among others) collectively lost $17.5 billion in one day. This isn’t the first time Amazon has disrupted the health care world; in January of this year, they, along with Berkshire Hathaway and JPMorgan Chase, announced a health care partnership to cut costs and improve care delivery for their employees. This move also sent shivers through the market, as health insurers and providers such as Aetna and United Health lost big on expectations that Amazon et al. wouldn’t stop with their own employees. Those of us watching this play out from the sidelines realized we were witnessing a revolution that would mean the end of health care delivery as we know it – and that’s not necessarily a bad thing, especially in the world of Electronic Health Records.

As you’ve probably noticed, it is quite rare to find physicians nowadays who love computers. Once an exciting novelty in health care, PCs have become a burdensome necessity and providers often feel enslaved to the EHRs that run on them. There are numerous reasons for this, but one primary cause is that the hundreds of disparate EHRs currently available sprouted out of health care – a centuries-old and very provincial industry – prior to the development of technical and regulatory standards to govern them. As they’ve grown larger and larger from their primitive underpinnings, these EHRs have become more cumbersome to navigate, and vendors have simply “bolted-on” additional features without significant changes to their near-obsolete software architecture.

It’s worth noting that a few EHR companies purport to be true innovators in platform usability, such as industry giant, Epic. According to CEO Judy Faulkner, Epic pours 50% of their revenue back into research and development (though, as Epic is a privately held company, this number can’t be verified). If accurate, Epic is truly an exception, as most electronic record companies spend about 10%-30% on improving their products – far less than they spend on recruiting new customers. Regardless, the outcome is this: Physician expectations for user interface and user experience have far outpaced the current state of the art of EHRs, and this has left a gap that new players outside the health care establishment are apt to fill.

Like Amazon, other software giants have made significant investments in health care over the past several years. According to their website, Apple has been working with hospitals, scientists, and developers to “help health care providers streamline their work, deliver better care, and conduct medical research.” Similarly, Google claims to be “making a number of big bets in health care and life sciences,” by leveraging their artificial intelligence technology to assist in clinical diagnosis and scientific discovery. In spite of a few false starts in the past, these companies are poised to do more than simply disrupt health care. As experts in user interface and design, they could truly change the way physicians interact with health care technology, and it seems like it’s no longer a question of if, but when we’ll see that happen.

The effort of SpaceX and others to change the way we launch rockets tells a story that transcends space travel – It’s a story of how new thinking, more efficient processes, and better design can disrupt the establishment. It’s worth pointing out that NASA hasn’t given up – they are continuing to develop the Space Launch System, which, when completed, will be the most powerful rocket in the world and be capable of carrying astronauts into deep space. In the meantime, however, NASA is embracing the efforts of private industry to help pave a better way forward and make space travel safer and more accessible for everyone. We are hopeful that EHR vendors and other establishment health care institutions are taking note, adapting to meet the needs of the current generation of physicians and patients, and innovating a better way to launch health care into the future.


 

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

On Friday, June 29, at 5:42 a.m., I stood with my family on a Florida shore overlooking Kennedy Space Center. We had gathered with about a hundred other people to watch a rocket launch and were overwhelmed with excitement as the coastline erupted in fire, and the spacecraft lifted off toward the heavens. Standing there watching the spectacle, I couldn’t help but be caught up in the irony of the moment. Here we were, at the place where NASA sent the first Americans into space – on the very shores where the Apollo astronauts set off for the moon to plant our nation’s flag in the lunar dust in July of 1969. Yet now, almost 50 years later, this launch was profoundly different. The rocket wasn’t built by NASA, and the intention of its builders wasn’t exploration. This was a Falcon 9, built by SpaceX, a for-profit company founded by an enterprising billionaire. Most surprisingly, this relatively routine launch was intended to accomplish something that NASA – the United States’ own space agency – currently can’t do on its own: Launch rockets.

Since retiring the Space Shuttle in 2011, the United States has had to rely on others – including even Roscosmos (the Russian space agency) – to ferry passengers, satellites, and cargo into space. Seeing this opportunity in a multibillion-dollar industry, private enterprise has risen to the challenge, innovating more quickly and at a lower cost than “the establishment” has ever been capable of. As a result, space travel has been disrupted by corporations competing in a new “space race.” Instead of national pride or scientific dominance, this race has been fueled by profit and is quite similar to one being run in another industry: health care.

Just 1 day prior to watching the launch – on June 28 – we learned that Amazon had purchased PillPack, a prescription drug home delivery service. The stock market responded to the news, and the establishment (in this case CVS, Walgreen’s, and WalMart, among others) collectively lost $17.5 billion in one day. This isn’t the first time Amazon has disrupted the health care world; in January of this year, they, along with Berkshire Hathaway and JPMorgan Chase, announced a health care partnership to cut costs and improve care delivery for their employees. This move also sent shivers through the market, as health insurers and providers such as Aetna and United Health lost big on expectations that Amazon et al. wouldn’t stop with their own employees. Those of us watching this play out from the sidelines realized we were witnessing a revolution that would mean the end of health care delivery as we know it – and that’s not necessarily a bad thing, especially in the world of Electronic Health Records.

As you’ve probably noticed, it is quite rare to find physicians nowadays who love computers. Once an exciting novelty in health care, PCs have become a burdensome necessity and providers often feel enslaved to the EHRs that run on them. There are numerous reasons for this, but one primary cause is that the hundreds of disparate EHRs currently available sprouted out of health care – a centuries-old and very provincial industry – prior to the development of technical and regulatory standards to govern them. As they’ve grown larger and larger from their primitive underpinnings, these EHRs have become more cumbersome to navigate, and vendors have simply “bolted-on” additional features without significant changes to their near-obsolete software architecture.

It’s worth noting that a few EHR companies purport to be true innovators in platform usability, such as industry giant, Epic. According to CEO Judy Faulkner, Epic pours 50% of their revenue back into research and development (though, as Epic is a privately held company, this number can’t be verified). If accurate, Epic is truly an exception, as most electronic record companies spend about 10%-30% on improving their products – far less than they spend on recruiting new customers. Regardless, the outcome is this: Physician expectations for user interface and user experience have far outpaced the current state of the art of EHRs, and this has left a gap that new players outside the health care establishment are apt to fill.

Like Amazon, other software giants have made significant investments in health care over the past several years. According to their website, Apple has been working with hospitals, scientists, and developers to “help health care providers streamline their work, deliver better care, and conduct medical research.” Similarly, Google claims to be “making a number of big bets in health care and life sciences,” by leveraging their artificial intelligence technology to assist in clinical diagnosis and scientific discovery. In spite of a few false starts in the past, these companies are poised to do more than simply disrupt health care. As experts in user interface and design, they could truly change the way physicians interact with health care technology, and it seems like it’s no longer a question of if, but when we’ll see that happen.

The effort of SpaceX and others to change the way we launch rockets tells a story that transcends space travel – It’s a story of how new thinking, more efficient processes, and better design can disrupt the establishment. It’s worth pointing out that NASA hasn’t given up – they are continuing to develop the Space Launch System, which, when completed, will be the most powerful rocket in the world and be capable of carrying astronauts into deep space. In the meantime, however, NASA is embracing the efforts of private industry to help pave a better way forward and make space travel safer and more accessible for everyone. We are hopeful that EHR vendors and other establishment health care institutions are taking note, adapting to meet the needs of the current generation of physicians and patients, and innovating a better way to launch health care into the future.


 

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

“Was this your first one?”

You might be asked this question in several circumstances. Was this your first 5K run? Was this your first time taking the MCAT? For me, I was asked if this was the first time a patient had died while in my care as a resident.

As it turns out, this was the first patient who died under my care. This seemed obvious to everyone around me because when I received the news, offhandedly, days after my patient’s discharge, I cried. My colleagues’ responses to my tears were kind and supportive. No one was callous or judgmental. I was given time to compose myself before continuing my rounds for the day. Yet, the most common question asked of me was, “Was this your first one?”

The implication of this question was that these situations would become easier and less emotional over time. Everyone believed my tears were a special response, privileged only to my first experience. This was conveyed to me as if it was a chance to explain my emotions. As if grieving alone was not sufficient to explain tears, I began to run through the reasons for my behavior, and my mind rapidly searched for answers. I thought:

• “I saw this patient daily for weeks, and I was close to him.”
• “There was an element of suicidality in this case, so it was different.”
• “After all, this was my first experience like this.”

In reality, these reasons were irrelevant and not needed to explain my tears. I was mourning the loss of a life—someone I had come to know well—and this was a life that ultimately could not be saved by the health care system.

These were my feelings during the July of my intern year. It is now a year later; I have since experienced an incredible number of moments that warranted mourning. There were oncology patients with advanced diseases who needed help disclosing their prognosis to family members. There were days when I was tasked with altering treatment courses from aggressive treatment to comfort measures only. There was the Christmas Eve when a pair of brothers dropped off their elderly father in the emergency department because no one was able or willing to care for him at home.

These moments can come fast, and they occur more frequently than one might imagine. Each is worthy of mourning. Each is worthy of tears, whether it is my first loss or my 50th. But the reality is that I could not function in my job and care for all my patients equally if I stopped every time to acknowledge my emotions. As much as it causes my stomach to turn, I understand the “Was this your first one?” phenomenon. To outwardly express your emotions and openly mourn in the moment, you need to have the time and allow yourself the vulnerability to do so. After your “first one,” you realize that mournful moments can occur regularly and you must choose to process emotions on your own time because you don’t have the luxury of processing a loss of life in the present moment.

Continue to: This is not to diminish...

This is not to diminish the importance of mourning or belittle the experience of processing one’s emotions. It simply highlights the importance of self-care. Emotions need to be processed outside of the hustle and bustle of the work day. There are other patients who require and deserve their clinician’s undivided attention. To truly provide patients with the highest quality of care, I find caring for myself and processing my reactions to daily events to be essential. Writing down my thoughts or talking to loved ones are ways that help me process my experiences. Taking a trip out of town, going for a hike, or watching a movie also are ways to help create balance in an emotionally charged career. I hope to use my new understanding of the “first one” phenomenon as a reminder to maintain my own well-being. In doing so, I can be attuned to my patients’ needs and provide them with empathic care. Even though my outward expression may change as I learn to process these moments differently, I want to treat each patient with the same level of empathy, value, and compassion as my first one.

“Was this your first one?”

You might be asked this question in several circumstances. Was this your first 5K run? Was this your first time taking the MCAT? For me, I was asked if this was the first time a patient had died while in my care as a resident.

As it turns out, this was the first patient who died under my care. This seemed obvious to everyone around me because when I received the news, offhandedly, days after my patient’s discharge, I cried. My colleagues’ responses to my tears were kind and supportive. No one was callous or judgmental. I was given time to compose myself before continuing my rounds for the day. Yet, the most common question asked of me was, “Was this your first one?”

The implication of this question was that these situations would become easier and less emotional over time. Everyone believed my tears were a special response, privileged only to my first experience. This was conveyed to me as if it was a chance to explain my emotions. As if grieving alone was not sufficient to explain tears, I began to run through the reasons for my behavior, and my mind rapidly searched for answers. I thought:

• “I saw this patient daily for weeks, and I was close to him.”
• “There was an element of suicidality in this case, so it was different.”
• “After all, this was my first experience like this.”

In reality, these reasons were irrelevant and not needed to explain my tears. I was mourning the loss of a life—someone I had come to know well—and this was a life that ultimately could not be saved by the health care system.

These were my feelings during the July of my intern year. It is now a year later; I have since experienced an incredible number of moments that warranted mourning. There were oncology patients with advanced diseases who needed help disclosing their prognosis to family members. There were days when I was tasked with altering treatment courses from aggressive treatment to comfort measures only. There was the Christmas Eve when a pair of brothers dropped off their elderly father in the emergency department because no one was able or willing to care for him at home.

These moments can come fast, and they occur more frequently than one might imagine. Each is worthy of mourning. Each is worthy of tears, whether it is my first loss or my 50th. But the reality is that I could not function in my job and care for all my patients equally if I stopped every time to acknowledge my emotions. As much as it causes my stomach to turn, I understand the “Was this your first one?” phenomenon. To outwardly express your emotions and openly mourn in the moment, you need to have the time and allow yourself the vulnerability to do so. After your “first one,” you realize that mournful moments can occur regularly and you must choose to process emotions on your own time because you don’t have the luxury of processing a loss of life in the present moment.

Continue to: This is not to diminish...

This is not to diminish the importance of mourning or belittle the experience of processing one’s emotions. It simply highlights the importance of self-care. Emotions need to be processed outside of the hustle and bustle of the work day. There are other patients who require and deserve their clinician’s undivided attention. To truly provide patients with the highest quality of care, I find caring for myself and processing my reactions to daily events to be essential. Writing down my thoughts or talking to loved ones are ways that help me process my experiences. Taking a trip out of town, going for a hike, or watching a movie also are ways to help create balance in an emotionally charged career. I hope to use my new understanding of the “first one” phenomenon as a reminder to maintain my own well-being. In doing so, I can be attuned to my patients’ needs and provide them with empathic care. Even though my outward expression may change as I learn to process these moments differently, I want to treat each patient with the same level of empathy, value, and compassion as my first one.

“Was this your first one?”

You might be asked this question in several circumstances. Was this your first 5K run? Was this your first time taking the MCAT? For me, I was asked if this was the first time a patient had died while in my care as a resident.

As it turns out, this was the first patient who died under my care. This seemed obvious to everyone around me because when I received the news, offhandedly, days after my patient’s discharge, I cried. My colleagues’ responses to my tears were kind and supportive. No one was callous or judgmental. I was given time to compose myself before continuing my rounds for the day. Yet, the most common question asked of me was, “Was this your first one?”

The implication of this question was that these situations would become easier and less emotional over time. Everyone believed my tears were a special response, privileged only to my first experience. This was conveyed to me as if it was a chance to explain my emotions. As if grieving alone was not sufficient to explain tears, I began to run through the reasons for my behavior, and my mind rapidly searched for answers. I thought:

• “I saw this patient daily for weeks, and I was close to him.”
• “There was an element of suicidality in this case, so it was different.”
• “After all, this was my first experience like this.”

In reality, these reasons were irrelevant and not needed to explain my tears. I was mourning the loss of a life—someone I had come to know well—and this was a life that ultimately could not be saved by the health care system.

These were my feelings during the July of my intern year. It is now a year later; I have since experienced an incredible number of moments that warranted mourning. There were oncology patients with advanced diseases who needed help disclosing their prognosis to family members. There were days when I was tasked with altering treatment courses from aggressive treatment to comfort measures only. There was the Christmas Eve when a pair of brothers dropped off their elderly father in the emergency department because no one was able or willing to care for him at home.

These moments can come fast, and they occur more frequently than one might imagine. Each is worthy of mourning. Each is worthy of tears, whether it is my first loss or my 50th. But the reality is that I could not function in my job and care for all my patients equally if I stopped every time to acknowledge my emotions. As much as it causes my stomach to turn, I understand the “Was this your first one?” phenomenon. To outwardly express your emotions and openly mourn in the moment, you need to have the time and allow yourself the vulnerability to do so. After your “first one,” you realize that mournful moments can occur regularly and you must choose to process emotions on your own time because you don’t have the luxury of processing a loss of life in the present moment.

Continue to: This is not to diminish...

This is not to diminish the importance of mourning or belittle the experience of processing one’s emotions. It simply highlights the importance of self-care. Emotions need to be processed outside of the hustle and bustle of the work day. There are other patients who require and deserve their clinician’s undivided attention. To truly provide patients with the highest quality of care, I find caring for myself and processing my reactions to daily events to be essential. Writing down my thoughts or talking to loved ones are ways that help me process my experiences. Taking a trip out of town, going for a hike, or watching a movie also are ways to help create balance in an emotionally charged career. I hope to use my new understanding of the “first one” phenomenon as a reminder to maintain my own well-being. In doing so, I can be attuned to my patients’ needs and provide them with empathic care. Even though my outward expression may change as I learn to process these moments differently, I want to treat each patient with the same level of empathy, value, and compassion as my first one.