SNOWMASS, COLO. – Cardiac MRI is the go-to tiebreaker when uncertainty exists as to whether cardiac remodeling in a competitive athlete is physiological or pathological, according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.

Bruce Jancin/MDedge News

“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.

But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?

“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.

In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.

“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.

He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).

That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”

Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.

“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.

Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.

“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.

Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.

“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.

Dr. Martinez reported having no financial conflicts of interest regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – Cardiac MRI is the go-to tiebreaker when uncertainty exists as to whether cardiac remodeling in a competitive athlete is physiological or pathological, according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.

Bruce Jancin/MDedge News

“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.

But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?

“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.

In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.

“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.

He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).

That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”

Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.

“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.

Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.

“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.

Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.

“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.

Dr. Martinez reported having no financial conflicts of interest regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – Cardiac MRI is the go-to tiebreaker when uncertainty exists as to whether cardiac remodeling in a competitive athlete is physiological or pathological, according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.

Bruce Jancin/MDedge News

“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.

But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?

“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.

In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.

“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.

He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).

That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”

Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.

“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.

Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.

“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.

Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.

“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.

Dr. Martinez reported having no financial conflicts of interest regarding his presentation.

bjancin@mdedge.com

Case Presentation

An 80-year-old white male was evaluated in a primary care clinic following a recent hospitalization for a suicide attempt. His past medical history included type 2 diabetes mellitus, chronic atrial fibrillation, essential hypertension and hyperlipidemia, and no prior psychiatric illness. Six weeks after his wife died of cancer, the patient attempted suicide by slitting his wrists, which resulted in significant blood loss and tendon damage.

After medical stabilization he was treated at an inpatient psychiatric facility for 10 days. There was no evidence of impaired memory nor psychosis during his hospitalization. He was prescribed doxazosin 1 mg twice daily and finasteride 5 mg daily for obstructive urinary symptoms, along with escitalopram 5 mg daily for depression and continuation of prior medications, including glipizide 10 mg twice daily, simvastatin 20 mg daily, metformin 500 mg twice daily, and lisinopril 20 mg daily. The patient’s estimated glomerular filtration rate was 85 at the time of these events.

He was evaluated by the mental health staff at the time of his primary care outpatient visit and noted to have a Patient Health Questionnaire (PHQ-9) score of 5 (mild depression symptoms) and a Generalized Anxiety Disorder 7 Item Scale (GAD-7) score of 1 (minimum anxiety symptoms). Eleven days later during his counseling appointment, he mentioned to staff that he had experienced a painful erection the day before, which lasted 4 hours. The primary care pharmacist was consulted for review of potential medication triggers. It was noted that there was a low frequency of priapism with both doxazosin and escitalopram, a selective serotonin reuptake inhibitor (SSRI). The provider team felt that the α blocker (doxazosin) was more likely than was the SSRI to cause the reported priapism event. Doxazosin was discontinued, and escitalopram 5 mg daily was maintained. His mood remained stable with no further suicidal ideation.

Eighteen days after discontinuation of doxazosin, the patient experienced a second priapism episode. He reported 2 days later that he experienced a prolonged, painful erection that lasted 4 hours and resolved without intervention. The patient’s mood continued without further suicidal thoughts, his appetite was normal, he had good social support and played cards with friends regularly. At that time, the decision was made to discontinue the escitalopram. The SSRI was felt to be a possible cause of priapism due to the length of time off doxazosin in relation to the second event.

The patient continued to do well 15 months after discontinuation of these medications. Unfortunately, he did not seek medical care during either episode of priapism, but he was felt to be reliable in his report based on a normal mental status exam. He does not have any of the other known risk factors for priapism, suggesting a possible association with his α blocker and SSRI.

Discussion

Priapism is a prolonged, painful erection lasting more than 4 hours and is considered a urologic emergency. It is divided into ischemic and nonischemic types. Ischemic priapism occurs with blood dyscrasias, such as sickle cell disease, thalassemia, leukemia, neurologic conditions affecting the spinal cord, and malignancies of bladder/prostate. The lifetime probability of priapism in patients affected by sickle cell disease is estimated at 29% to 42%.¹ Medications associated with priapism include cocaine, ondansetron, antipsychotics, excessive use of erectile dysfunction drugs, and increasingly, antidepressants.^2-8

Nonischemic priapism is usually associated with pelvic trauma. Cavernous blood gas obtained at the time of the event can help distinguish between the 2 types. The color of the aspirated blood sample is black in patients with ischemic priapism. Corporal blood gas analysis shows hypoxemia and acidemia. The color of blood is red in patients with nonischemic priapism and shows normal oxygen and pH. Priapism is a urologic emergency requiring aspiration of blood from the cavernous sinus to prevent ischemic tissue damage. At times surgical decompression may be required if aspiration is not successful.

Adrenergic α-blocking agents were developed for treatment of hypertension. They have become popular for management of lower urinary tract symptoms (LUTS) secondary to prostate enlargement. Doxazosin, prazosin, and terazosin are nonuroselective and have a higher risk of cardiac adverse effects (AEs), including dizziness and orthostatic hypotension. Lexicomp lists < 1% incidence of priapism associated with doxazosin.⁹ The drug is metabolized by CYP3A4 with secondary pathways, including CYP2D6 and 2C9 with a drug half-life of 22 hours. Newer agents (eg, tamsulosin, alfuzosin) are considered more uroselective, targeting the α-1b receptors. The older agents have more effect on the α-1a receptors, which are also present at higher level in the cardiovascular system.¹⁰ By blocking sympathetic stimuli responsible for penile detumescence, the nonselective α blockers have a higher propensity to cause priapism. There seems to be a direct correlation between higher doses and increased risk of priapism.¹¹ Our patient was at a relatively low dose (1 mg twice daily) of the nonselective agent doxazosin for treatment of his LUTS.

Primary care providers and psychiatrists treating depression are familiar with common sexual AEs of the SSRI class of medications. Decreased sexual desire and delayed orgasm and ejaculation are all issues that lead patients to discontinue treatment. Although SSRIs are considered first-line treatment for depression, reports indicate that up to 60% of patients with prior normal sexual function started on paroxetine may experience sexual AEs.¹² The exact frequency is difficult to estimate due to underreporting of these issues by patients.

A review of the literature for cases of priapism associated with SSRIs shows that often there is more than 1 possible drug trigger, and medications used in combination may be a risk factor. It is hypothesized that SSRI action on 5-HT3 receptors may be responsible for priapism occurring in patients treated with SSRIs.¹³ One study cites a case of priapism in a veteran being treated with escitalopram, prazosin, and trazodone for posttraumatic stress disorder.¹⁴ Trazodone inhibits the neuronal uptake of serotonin and is used to treat depression in addition to off-label use in treatment of insomnia. Trazodone is implicated in cases of priapism via its α-blocking properties. In the aforementioned case, trazodone was initially thought to be the causative agent and was discontinued. The patient had recurrent symptoms at which time his prazosin was discontinued, and he had no further events.

Another case cites citalopram-induced priapism that occurred with an accidental overdose of citalopram 80 mg, when a patient confused his antidepressant with 81-mg aspirin tablets.¹⁵ He also had a prior history of priapism while taking trazodone. We found only 1 case listing escitalopram as the probable causative agent of priapism.¹⁶ Similar to our patient, that case had no risk factors prior to escitalopram administration. Lexicomp notes < 1% incidence of priapism reported in postmarketing studies.

Our patient had been off doxazosin for 18 days when his second event of priapism occurred. It is less likely given the half-life of doxazosin (t ½ = 22 hours) that the α blocker was the causative agent, though a combination of the 2 agents cannot be excluded as a significant factor. The Naranjo Score is an algorithm for determining the likelihood of whether an adverse drug reaction is due to the drug or other factors.¹⁷ Scoring ranks the event as probable, possible, or doubtful. This case scored +3 (+2 = appeared after suspected drug given, +1 = improved when drug discontinued), indicating possible association of escitalopram and priapism.

Conclusion

In view of the frequent use of SSRIs in treatment of depression, it may be prudent to advise patients of this uncommon but serious medication AE. Recent use of α blockers may be a risk factor in combination with SSRI therapy. Patients should be counseled to seek emergency care in the event of prolonged erection when discussing potential AEs of SSRI therapy.

Case Presentation

An 80-year-old white male was evaluated in a primary care clinic following a recent hospitalization for a suicide attempt. His past medical history included type 2 diabetes mellitus, chronic atrial fibrillation, essential hypertension and hyperlipidemia, and no prior psychiatric illness. Six weeks after his wife died of cancer, the patient attempted suicide by slitting his wrists, which resulted in significant blood loss and tendon damage.

After medical stabilization he was treated at an inpatient psychiatric facility for 10 days. There was no evidence of impaired memory nor psychosis during his hospitalization. He was prescribed doxazosin 1 mg twice daily and finasteride 5 mg daily for obstructive urinary symptoms, along with escitalopram 5 mg daily for depression and continuation of prior medications, including glipizide 10 mg twice daily, simvastatin 20 mg daily, metformin 500 mg twice daily, and lisinopril 20 mg daily. The patient’s estimated glomerular filtration rate was 85 at the time of these events.

He was evaluated by the mental health staff at the time of his primary care outpatient visit and noted to have a Patient Health Questionnaire (PHQ-9) score of 5 (mild depression symptoms) and a Generalized Anxiety Disorder 7 Item Scale (GAD-7) score of 1 (minimum anxiety symptoms). Eleven days later during his counseling appointment, he mentioned to staff that he had experienced a painful erection the day before, which lasted 4 hours. The primary care pharmacist was consulted for review of potential medication triggers. It was noted that there was a low frequency of priapism with both doxazosin and escitalopram, a selective serotonin reuptake inhibitor (SSRI). The provider team felt that the α blocker (doxazosin) was more likely than was the SSRI to cause the reported priapism event. Doxazosin was discontinued, and escitalopram 5 mg daily was maintained. His mood remained stable with no further suicidal ideation.

Eighteen days after discontinuation of doxazosin, the patient experienced a second priapism episode. He reported 2 days later that he experienced a prolonged, painful erection that lasted 4 hours and resolved without intervention. The patient’s mood continued without further suicidal thoughts, his appetite was normal, he had good social support and played cards with friends regularly. At that time, the decision was made to discontinue the escitalopram. The SSRI was felt to be a possible cause of priapism due to the length of time off doxazosin in relation to the second event.

The patient continued to do well 15 months after discontinuation of these medications. Unfortunately, he did not seek medical care during either episode of priapism, but he was felt to be reliable in his report based on a normal mental status exam. He does not have any of the other known risk factors for priapism, suggesting a possible association with his α blocker and SSRI.

Discussion

Priapism is a prolonged, painful erection lasting more than 4 hours and is considered a urologic emergency. It is divided into ischemic and nonischemic types. Ischemic priapism occurs with blood dyscrasias, such as sickle cell disease, thalassemia, leukemia, neurologic conditions affecting the spinal cord, and malignancies of bladder/prostate. The lifetime probability of priapism in patients affected by sickle cell disease is estimated at 29% to 42%.¹ Medications associated with priapism include cocaine, ondansetron, antipsychotics, excessive use of erectile dysfunction drugs, and increasingly, antidepressants.^2-8

Nonischemic priapism is usually associated with pelvic trauma. Cavernous blood gas obtained at the time of the event can help distinguish between the 2 types. The color of the aspirated blood sample is black in patients with ischemic priapism. Corporal blood gas analysis shows hypoxemia and acidemia. The color of blood is red in patients with nonischemic priapism and shows normal oxygen and pH. Priapism is a urologic emergency requiring aspiration of blood from the cavernous sinus to prevent ischemic tissue damage. At times surgical decompression may be required if aspiration is not successful.

Adrenergic α-blocking agents were developed for treatment of hypertension. They have become popular for management of lower urinary tract symptoms (LUTS) secondary to prostate enlargement. Doxazosin, prazosin, and terazosin are nonuroselective and have a higher risk of cardiac adverse effects (AEs), including dizziness and orthostatic hypotension. Lexicomp lists < 1% incidence of priapism associated with doxazosin.⁹ The drug is metabolized by CYP3A4 with secondary pathways, including CYP2D6 and 2C9 with a drug half-life of 22 hours. Newer agents (eg, tamsulosin, alfuzosin) are considered more uroselective, targeting the α-1b receptors. The older agents have more effect on the α-1a receptors, which are also present at higher level in the cardiovascular system.¹⁰ By blocking sympathetic stimuli responsible for penile detumescence, the nonselective α blockers have a higher propensity to cause priapism. There seems to be a direct correlation between higher doses and increased risk of priapism.¹¹ Our patient was at a relatively low dose (1 mg twice daily) of the nonselective agent doxazosin for treatment of his LUTS.

Primary care providers and psychiatrists treating depression are familiar with common sexual AEs of the SSRI class of medications. Decreased sexual desire and delayed orgasm and ejaculation are all issues that lead patients to discontinue treatment. Although SSRIs are considered first-line treatment for depression, reports indicate that up to 60% of patients with prior normal sexual function started on paroxetine may experience sexual AEs.¹² The exact frequency is difficult to estimate due to underreporting of these issues by patients.

A review of the literature for cases of priapism associated with SSRIs shows that often there is more than 1 possible drug trigger, and medications used in combination may be a risk factor. It is hypothesized that SSRI action on 5-HT3 receptors may be responsible for priapism occurring in patients treated with SSRIs.¹³ One study cites a case of priapism in a veteran being treated with escitalopram, prazosin, and trazodone for posttraumatic stress disorder.¹⁴ Trazodone inhibits the neuronal uptake of serotonin and is used to treat depression in addition to off-label use in treatment of insomnia. Trazodone is implicated in cases of priapism via its α-blocking properties. In the aforementioned case, trazodone was initially thought to be the causative agent and was discontinued. The patient had recurrent symptoms at which time his prazosin was discontinued, and he had no further events.

Another case cites citalopram-induced priapism that occurred with an accidental overdose of citalopram 80 mg, when a patient confused his antidepressant with 81-mg aspirin tablets.¹⁵ He also had a prior history of priapism while taking trazodone. We found only 1 case listing escitalopram as the probable causative agent of priapism.¹⁶ Similar to our patient, that case had no risk factors prior to escitalopram administration. Lexicomp notes < 1% incidence of priapism reported in postmarketing studies.

Our patient had been off doxazosin for 18 days when his second event of priapism occurred. It is less likely given the half-life of doxazosin (t ½ = 22 hours) that the α blocker was the causative agent, though a combination of the 2 agents cannot be excluded as a significant factor. The Naranjo Score is an algorithm for determining the likelihood of whether an adverse drug reaction is due to the drug or other factors.¹⁷ Scoring ranks the event as probable, possible, or doubtful. This case scored +3 (+2 = appeared after suspected drug given, +1 = improved when drug discontinued), indicating possible association of escitalopram and priapism.

Conclusion

In view of the frequent use of SSRIs in treatment of depression, it may be prudent to advise patients of this uncommon but serious medication AE. Recent use of α blockers may be a risk factor in combination with SSRI therapy. Patients should be counseled to seek emergency care in the event of prolonged erection when discussing potential AEs of SSRI therapy.

Case Presentation

An 80-year-old white male was evaluated in a primary care clinic following a recent hospitalization for a suicide attempt. His past medical history included type 2 diabetes mellitus, chronic atrial fibrillation, essential hypertension and hyperlipidemia, and no prior psychiatric illness. Six weeks after his wife died of cancer, the patient attempted suicide by slitting his wrists, which resulted in significant blood loss and tendon damage.

After medical stabilization he was treated at an inpatient psychiatric facility for 10 days. There was no evidence of impaired memory nor psychosis during his hospitalization. He was prescribed doxazosin 1 mg twice daily and finasteride 5 mg daily for obstructive urinary symptoms, along with escitalopram 5 mg daily for depression and continuation of prior medications, including glipizide 10 mg twice daily, simvastatin 20 mg daily, metformin 500 mg twice daily, and lisinopril 20 mg daily. The patient’s estimated glomerular filtration rate was 85 at the time of these events.

He was evaluated by the mental health staff at the time of his primary care outpatient visit and noted to have a Patient Health Questionnaire (PHQ-9) score of 5 (mild depression symptoms) and a Generalized Anxiety Disorder 7 Item Scale (GAD-7) score of 1 (minimum anxiety symptoms). Eleven days later during his counseling appointment, he mentioned to staff that he had experienced a painful erection the day before, which lasted 4 hours. The primary care pharmacist was consulted for review of potential medication triggers. It was noted that there was a low frequency of priapism with both doxazosin and escitalopram, a selective serotonin reuptake inhibitor (SSRI). The provider team felt that the α blocker (doxazosin) was more likely than was the SSRI to cause the reported priapism event. Doxazosin was discontinued, and escitalopram 5 mg daily was maintained. His mood remained stable with no further suicidal ideation.

Eighteen days after discontinuation of doxazosin, the patient experienced a second priapism episode. He reported 2 days later that he experienced a prolonged, painful erection that lasted 4 hours and resolved without intervention. The patient’s mood continued without further suicidal thoughts, his appetite was normal, he had good social support and played cards with friends regularly. At that time, the decision was made to discontinue the escitalopram. The SSRI was felt to be a possible cause of priapism due to the length of time off doxazosin in relation to the second event.

The patient continued to do well 15 months after discontinuation of these medications. Unfortunately, he did not seek medical care during either episode of priapism, but he was felt to be reliable in his report based on a normal mental status exam. He does not have any of the other known risk factors for priapism, suggesting a possible association with his α blocker and SSRI.

Discussion

Priapism is a prolonged, painful erection lasting more than 4 hours and is considered a urologic emergency. It is divided into ischemic and nonischemic types. Ischemic priapism occurs with blood dyscrasias, such as sickle cell disease, thalassemia, leukemia, neurologic conditions affecting the spinal cord, and malignancies of bladder/prostate. The lifetime probability of priapism in patients affected by sickle cell disease is estimated at 29% to 42%.¹ Medications associated with priapism include cocaine, ondansetron, antipsychotics, excessive use of erectile dysfunction drugs, and increasingly, antidepressants.^2-8

Nonischemic priapism is usually associated with pelvic trauma. Cavernous blood gas obtained at the time of the event can help distinguish between the 2 types. The color of the aspirated blood sample is black in patients with ischemic priapism. Corporal blood gas analysis shows hypoxemia and acidemia. The color of blood is red in patients with nonischemic priapism and shows normal oxygen and pH. Priapism is a urologic emergency requiring aspiration of blood from the cavernous sinus to prevent ischemic tissue damage. At times surgical decompression may be required if aspiration is not successful.

Adrenergic α-blocking agents were developed for treatment of hypertension. They have become popular for management of lower urinary tract symptoms (LUTS) secondary to prostate enlargement. Doxazosin, prazosin, and terazosin are nonuroselective and have a higher risk of cardiac adverse effects (AEs), including dizziness and orthostatic hypotension. Lexicomp lists < 1% incidence of priapism associated with doxazosin.⁹ The drug is metabolized by CYP3A4 with secondary pathways, including CYP2D6 and 2C9 with a drug half-life of 22 hours. Newer agents (eg, tamsulosin, alfuzosin) are considered more uroselective, targeting the α-1b receptors. The older agents have more effect on the α-1a receptors, which are also present at higher level in the cardiovascular system.¹⁰ By blocking sympathetic stimuli responsible for penile detumescence, the nonselective α blockers have a higher propensity to cause priapism. There seems to be a direct correlation between higher doses and increased risk of priapism.¹¹ Our patient was at a relatively low dose (1 mg twice daily) of the nonselective agent doxazosin for treatment of his LUTS.

Primary care providers and psychiatrists treating depression are familiar with common sexual AEs of the SSRI class of medications. Decreased sexual desire and delayed orgasm and ejaculation are all issues that lead patients to discontinue treatment. Although SSRIs are considered first-line treatment for depression, reports indicate that up to 60% of patients with prior normal sexual function started on paroxetine may experience sexual AEs.¹² The exact frequency is difficult to estimate due to underreporting of these issues by patients.

A review of the literature for cases of priapism associated with SSRIs shows that often there is more than 1 possible drug trigger, and medications used in combination may be a risk factor. It is hypothesized that SSRI action on 5-HT3 receptors may be responsible for priapism occurring in patients treated with SSRIs.¹³ One study cites a case of priapism in a veteran being treated with escitalopram, prazosin, and trazodone for posttraumatic stress disorder.¹⁴ Trazodone inhibits the neuronal uptake of serotonin and is used to treat depression in addition to off-label use in treatment of insomnia. Trazodone is implicated in cases of priapism via its α-blocking properties. In the aforementioned case, trazodone was initially thought to be the causative agent and was discontinued. The patient had recurrent symptoms at which time his prazosin was discontinued, and he had no further events.

Another case cites citalopram-induced priapism that occurred with an accidental overdose of citalopram 80 mg, when a patient confused his antidepressant with 81-mg aspirin tablets.¹⁵ He also had a prior history of priapism while taking trazodone. We found only 1 case listing escitalopram as the probable causative agent of priapism.¹⁶ Similar to our patient, that case had no risk factors prior to escitalopram administration. Lexicomp notes < 1% incidence of priapism reported in postmarketing studies.

Our patient had been off doxazosin for 18 days when his second event of priapism occurred. It is less likely given the half-life of doxazosin (t ½ = 22 hours) that the α blocker was the causative agent, though a combination of the 2 agents cannot be excluded as a significant factor. The Naranjo Score is an algorithm for determining the likelihood of whether an adverse drug reaction is due to the drug or other factors.¹⁷ Scoring ranks the event as probable, possible, or doubtful. This case scored +3 (+2 = appeared after suspected drug given, +1 = improved when drug discontinued), indicating possible association of escitalopram and priapism.

Conclusion

In view of the frequent use of SSRIs in treatment of depression, it may be prudent to advise patients of this uncommon but serious medication AE. Recent use of α blockers may be a risk factor in combination with SSRI therapy. Patients should be counseled to seek emergency care in the event of prolonged erection when discussing potential AEs of SSRI therapy.

Patients infected with HIV have an increased risk of mortality and morbidity from diseases that are preventable with vaccines. Undervaccination of these patients poses a major concern, according to a literature review of the vaccine response in the adult patient with HIV published in The American Journal of Medicine.

copyright itsmejust/Thinkstock

Despite the fact that data are limited, patients infected with HIV are advised to receive their age-specific and risk group−based vaccines, according to Firas El Chaer, MD, of the University of Maryland, Baltimore, and his colleague.

HIV patients are of particular concern regarding vaccination, because, despite the use of retroviral therapy, CD4+ T-lymphocytes in individuals infected with HIV remain lower than in those without HIV. In addition, HIV causes an inappropriate response to B-cell stimulation, which results in suboptimal primary and secondary response to vaccination, according to Dr. El Chaer and his colleague. Despite this and initial concerns about vaccine safety in this population, it is now recommended that adult patients infected with HIV receive their age-specific and risk group−based vaccines, they stated.
 

Inactivated or subunit vaccines

Haemophilus influenzae type b vaccine is not recommended under current guidelines for individuals older than age 18 with HIV infection, unless they have a clinical indication.

Vaccination against hepatitis A virus is recommended for HIV-infected patients who are hepatitis A virus seronegative and have chronic liver disease, men who have sex with men, intravenous drug users, and travelers to endemic regions. However, research has shown that the immunogenicity of the vaccine is lower in patients with HIV than in uninfected individuals. It was found that the CD4 count at the time of vaccination, not the CD4 low point, was the major predictor of the immune response.

Patients coinfected with HIV and hepatitis B virus have an 8-fold and 19-fold increase in mortality, respectively, compared with either virus monoinfection. Although vaccination is recommended, the optimal hepatitis B virus vaccination schedule in patients with HIV remains controversial, according to the authors. They indicated that new strategies to improve hepatitis B virus vaccine immunogenicity for those infected with HIV are needed.

Individuals infected with HIV have been found to have a higher risk of human papillomavirus (HPV) infection. The safety and immunogenicity results and prospect of benefits has led to a consensus on the benefit of vaccinating HIV-infected patients who meet the HPV vaccine age criteria, the authors indicated.

With regard to standard flu vaccinations: “An annual inactivated influenza vaccine is recommended during the influenza season for all adult individuals with HIV; however, a live attenuated influenza vaccine is contraindicated in this population,” according to the review.

Patients with HIV have a more than 10-fold increased risk of invasive meningococcal disease, compared with the general population, with the risk being particularly higher in those individuals with CD4 counts less than 200 cells/mm³ and in men who have sex with men in cities with meningococcal outbreaks. For these reasons, the “quadrivalent meningococcal vaccine is recommended for all patients with HIV regardless of their CD4 count, with 2-dose primary series at least 2 months apart and with a booster every 5 years.”

Pneumonia is known to be especially dangerous in the HIV-infected population. With regard to pneumonia vaccination, the 13-valent pneumococcal conjugate vaccine is recommended for all patients with HIV, regardless of their CD4 cell counts. According to Dr. El Chaer and his colleague, it should be followed by the 23-valent pneumococcal polysaccharide vaccine at least 8 weeks later as a prime-boost regimen, preferably when CD4 counts are greater than 200 cells/mm³ and in patients receiving ART.

“Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines are recommended once for all individuals infected with HIV, regardless of the CD4 count, with a tetanus toxoid and diphtheria toxoid booster every 10 years,” according to the review.
 

Live vaccines

Live vaccines are a concerning issue for HIV-infected adults and recommendations for use are generally tied to the CD4 T-cell count. The measles, mumps, and rubella vaccine seems to be safe in patients infected with HIV with a CD4 count greater than 200 cells/mm³, according to Dr. El Chaer and his colleague. Similarly, patients with HIV with CD4 counts greater than 200 cells/mm³ and no evidence of documented immunity to varicella should receive the varicella vaccine.

In contrast, the live, attenuated varicella zoster virus vaccine is not recommended for patients infected with HIV, and it is contraindicated if CD4 count is less than 200 cells/mm³. Recently, a herpes zoster subunit vaccine (HZ/su) was tested in a phase 1/2a randomized, placebo-controlled study and was found to be safe and immunogenic regardless of CD4 count, although it has not yet been given a specific recommendation for immunocompromised patients.

“With the widespread use of ART resulting in better HIV control, clinical vaccine development plans should include patients with HIV and other at-risk populations because they often carry much of the disease burden,” the authors concluded.

The study was not sponsored. Dr. El Chaer and his colleague reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: El Chaer F et al. Am J Med. 2019. doi: 10.1016/j.amjmed.2018.12.011.

Patients infected with HIV have an increased risk of mortality and morbidity from diseases that are preventable with vaccines. Undervaccination of these patients poses a major concern, according to a literature review of the vaccine response in the adult patient with HIV published in The American Journal of Medicine.

copyright itsmejust/Thinkstock

Despite the fact that data are limited, patients infected with HIV are advised to receive their age-specific and risk group−based vaccines, according to Firas El Chaer, MD, of the University of Maryland, Baltimore, and his colleague.

HIV patients are of particular concern regarding vaccination, because, despite the use of retroviral therapy, CD4+ T-lymphocytes in individuals infected with HIV remain lower than in those without HIV. In addition, HIV causes an inappropriate response to B-cell stimulation, which results in suboptimal primary and secondary response to vaccination, according to Dr. El Chaer and his colleague. Despite this and initial concerns about vaccine safety in this population, it is now recommended that adult patients infected with HIV receive their age-specific and risk group−based vaccines, they stated.
 

Inactivated or subunit vaccines

Haemophilus influenzae type b vaccine is not recommended under current guidelines for individuals older than age 18 with HIV infection, unless they have a clinical indication.

Vaccination against hepatitis A virus is recommended for HIV-infected patients who are hepatitis A virus seronegative and have chronic liver disease, men who have sex with men, intravenous drug users, and travelers to endemic regions. However, research has shown that the immunogenicity of the vaccine is lower in patients with HIV than in uninfected individuals. It was found that the CD4 count at the time of vaccination, not the CD4 low point, was the major predictor of the immune response.

Patients coinfected with HIV and hepatitis B virus have an 8-fold and 19-fold increase in mortality, respectively, compared with either virus monoinfection. Although vaccination is recommended, the optimal hepatitis B virus vaccination schedule in patients with HIV remains controversial, according to the authors. They indicated that new strategies to improve hepatitis B virus vaccine immunogenicity for those infected with HIV are needed.

Individuals infected with HIV have been found to have a higher risk of human papillomavirus (HPV) infection. The safety and immunogenicity results and prospect of benefits has led to a consensus on the benefit of vaccinating HIV-infected patients who meet the HPV vaccine age criteria, the authors indicated.

With regard to standard flu vaccinations: “An annual inactivated influenza vaccine is recommended during the influenza season for all adult individuals with HIV; however, a live attenuated influenza vaccine is contraindicated in this population,” according to the review.

Patients with HIV have a more than 10-fold increased risk of invasive meningococcal disease, compared with the general population, with the risk being particularly higher in those individuals with CD4 counts less than 200 cells/mm³ and in men who have sex with men in cities with meningococcal outbreaks. For these reasons, the “quadrivalent meningococcal vaccine is recommended for all patients with HIV regardless of their CD4 count, with 2-dose primary series at least 2 months apart and with a booster every 5 years.”

Pneumonia is known to be especially dangerous in the HIV-infected population. With regard to pneumonia vaccination, the 13-valent pneumococcal conjugate vaccine is recommended for all patients with HIV, regardless of their CD4 cell counts. According to Dr. El Chaer and his colleague, it should be followed by the 23-valent pneumococcal polysaccharide vaccine at least 8 weeks later as a prime-boost regimen, preferably when CD4 counts are greater than 200 cells/mm³ and in patients receiving ART.

“Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines are recommended once for all individuals infected with HIV, regardless of the CD4 count, with a tetanus toxoid and diphtheria toxoid booster every 10 years,” according to the review.
 

Live vaccines

Live vaccines are a concerning issue for HIV-infected adults and recommendations for use are generally tied to the CD4 T-cell count. The measles, mumps, and rubella vaccine seems to be safe in patients infected with HIV with a CD4 count greater than 200 cells/mm³, according to Dr. El Chaer and his colleague. Similarly, patients with HIV with CD4 counts greater than 200 cells/mm³ and no evidence of documented immunity to varicella should receive the varicella vaccine.

In contrast, the live, attenuated varicella zoster virus vaccine is not recommended for patients infected with HIV, and it is contraindicated if CD4 count is less than 200 cells/mm³. Recently, a herpes zoster subunit vaccine (HZ/su) was tested in a phase 1/2a randomized, placebo-controlled study and was found to be safe and immunogenic regardless of CD4 count, although it has not yet been given a specific recommendation for immunocompromised patients.

“With the widespread use of ART resulting in better HIV control, clinical vaccine development plans should include patients with HIV and other at-risk populations because they often carry much of the disease burden,” the authors concluded.

The study was not sponsored. Dr. El Chaer and his colleague reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: El Chaer F et al. Am J Med. 2019. doi: 10.1016/j.amjmed.2018.12.011.

Patients infected with HIV have an increased risk of mortality and morbidity from diseases that are preventable with vaccines. Undervaccination of these patients poses a major concern, according to a literature review of the vaccine response in the adult patient with HIV published in The American Journal of Medicine.

copyright itsmejust/Thinkstock

Despite the fact that data are limited, patients infected with HIV are advised to receive their age-specific and risk group−based vaccines, according to Firas El Chaer, MD, of the University of Maryland, Baltimore, and his colleague.

HIV patients are of particular concern regarding vaccination, because, despite the use of retroviral therapy, CD4+ T-lymphocytes in individuals infected with HIV remain lower than in those without HIV. In addition, HIV causes an inappropriate response to B-cell stimulation, which results in suboptimal primary and secondary response to vaccination, according to Dr. El Chaer and his colleague. Despite this and initial concerns about vaccine safety in this population, it is now recommended that adult patients infected with HIV receive their age-specific and risk group−based vaccines, they stated.
 

Inactivated or subunit vaccines

Haemophilus influenzae type b vaccine is not recommended under current guidelines for individuals older than age 18 with HIV infection, unless they have a clinical indication.

Vaccination against hepatitis A virus is recommended for HIV-infected patients who are hepatitis A virus seronegative and have chronic liver disease, men who have sex with men, intravenous drug users, and travelers to endemic regions. However, research has shown that the immunogenicity of the vaccine is lower in patients with HIV than in uninfected individuals. It was found that the CD4 count at the time of vaccination, not the CD4 low point, was the major predictor of the immune response.

Patients coinfected with HIV and hepatitis B virus have an 8-fold and 19-fold increase in mortality, respectively, compared with either virus monoinfection. Although vaccination is recommended, the optimal hepatitis B virus vaccination schedule in patients with HIV remains controversial, according to the authors. They indicated that new strategies to improve hepatitis B virus vaccine immunogenicity for those infected with HIV are needed.

Individuals infected with HIV have been found to have a higher risk of human papillomavirus (HPV) infection. The safety and immunogenicity results and prospect of benefits has led to a consensus on the benefit of vaccinating HIV-infected patients who meet the HPV vaccine age criteria, the authors indicated.

With regard to standard flu vaccinations: “An annual inactivated influenza vaccine is recommended during the influenza season for all adult individuals with HIV; however, a live attenuated influenza vaccine is contraindicated in this population,” according to the review.

Patients with HIV have a more than 10-fold increased risk of invasive meningococcal disease, compared with the general population, with the risk being particularly higher in those individuals with CD4 counts less than 200 cells/mm³ and in men who have sex with men in cities with meningococcal outbreaks. For these reasons, the “quadrivalent meningococcal vaccine is recommended for all patients with HIV regardless of their CD4 count, with 2-dose primary series at least 2 months apart and with a booster every 5 years.”

Pneumonia is known to be especially dangerous in the HIV-infected population. With regard to pneumonia vaccination, the 13-valent pneumococcal conjugate vaccine is recommended for all patients with HIV, regardless of their CD4 cell counts. According to Dr. El Chaer and his colleague, it should be followed by the 23-valent pneumococcal polysaccharide vaccine at least 8 weeks later as a prime-boost regimen, preferably when CD4 counts are greater than 200 cells/mm³ and in patients receiving ART.

“Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines are recommended once for all individuals infected with HIV, regardless of the CD4 count, with a tetanus toxoid and diphtheria toxoid booster every 10 years,” according to the review.
 

Live vaccines

Live vaccines are a concerning issue for HIV-infected adults and recommendations for use are generally tied to the CD4 T-cell count. The measles, mumps, and rubella vaccine seems to be safe in patients infected with HIV with a CD4 count greater than 200 cells/mm³, according to Dr. El Chaer and his colleague. Similarly, patients with HIV with CD4 counts greater than 200 cells/mm³ and no evidence of documented immunity to varicella should receive the varicella vaccine.

In contrast, the live, attenuated varicella zoster virus vaccine is not recommended for patients infected with HIV, and it is contraindicated if CD4 count is less than 200 cells/mm³. Recently, a herpes zoster subunit vaccine (HZ/su) was tested in a phase 1/2a randomized, placebo-controlled study and was found to be safe and immunogenic regardless of CD4 count, although it has not yet been given a specific recommendation for immunocompromised patients.

“With the widespread use of ART resulting in better HIV control, clinical vaccine development plans should include patients with HIV and other at-risk populations because they often carry much of the disease burden,” the authors concluded.

The study was not sponsored. Dr. El Chaer and his colleague reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: El Chaer F et al. Am J Med. 2019. doi: 10.1016/j.amjmed.2018.12.011.

March often is the time of year when college freshmen truly begin to feel comfortable in their new settings. Many students report feeling excited to get back to campus after the long winter break, and once into their second semester, they feel more comfortable with the independence from family and high school supports. It also is a time for some college freshmen to return home after failing to manage this major transition.

SolStock/Getty Images

Of the latter group, many will have had difficult months of depression, anxiety, or substance use, and most will be suffering from a deep sense of shame after failing to navigate this long-anticipated transition. There are several reasons why some older adolescents fail to manage the transition to college, some more serious than others. Asking detailed questions about their academic challenges, social lives, self-care, and sleep while they were on campus will help you make thoughtful recommendations to your patients and their parents about how they might best get back on track.

Some students will report a great social experience, but academic struggles. They will report some normal ups and downs emotionally, but most of their distress will have been focused on their academic performance. Many 18-year-olds have not had to organize their time and effort around homework without the attention and support of parents and teachers. College often has much bigger classes, with less personal attention. There is a lot of assigned reading, but no regular incremental homework, only a major midterm and final exam, or a substantial paper. For a student who gets anxious about performance, or one with organizational challenges, this can lead to procrastination and poor performance.

Find out details about how they did academically. Did they fail one class or many classes? Did they receive some incompletes in their first semester and then struggle to catch up with them while keeping up with their second semester work? Did they have tutoring or support? Were they unrealistic about their course load? Or did they have their first serious relationship and not spend enough time on homework? Did they spend too much time partying with their new friends and not enough time sleeping and getting their homework done?

It is important to dig deeper if patients report regular or binge drug and alcohol use that interfered with their academic performance, as they may need more substantial substance use disorder treatment. Most students, though, will not have a substance use disorder. Instead, their academic failure could represent something as simple as the need for more academic support and time management support. Many schools have such programs to help students learn how to better manage their time and effort as they take fuller responsibility than they had for it in high school.

For other students, you will learn that their emotional distress preceded their academic troubles. The stress of the transition to college may be enough to trigger an episode of depression or to exacerbate a mood or anxiety disorder that was subclinical or in remission before school started. These students usually will report that sadness, intense anxiety, or loss of interest came early in their semester; perhaps they were even doing well academically when these problems started.

Ask about how their sleep was. Often they had difficulty falling asleep or woke up often at night, unlike most college students, whose sleep is compromised because they stay up late with new friends or because they are hard at work, but could easily sleep at any time.

Find out about their eating habits. Did they lose their appetite? Lose weight? Did they become preoccupied with weight or body image issues and begin restricting their intake? Eating disorders can begin in college when vulnerable students are stressed and have more control over their diet. While weight gain is more common in freshman year, it often is connected to poor stress management skills, and is more often a marker of a student who was struggling academically and then managing stress by overeating.

In the case where the distress came first, it is critical that your patients have a thorough psychiatric evaluation and treatment. It may be possible for them to return to school quickly, but it is most important that they are engaged in effective treatment and in at last partial remission before adding to their stress by attempting to return to school. Often, ambitious students and their parents need to hear this message very clearly from a pediatrician. A rushed return to school may be a set-up for a more protracted and difficult course of illness. For these students, it may be better to have a fresh start in a new semester. Help them (and their parents) to understand that they should use their time off to focus on treatment and good self-care so they might benefit from the many opportunities of college.

For a small minority of college students who do not succeed at college, their social withdrawal, academic deterioration, anxiety, and loss of interest in previous passions may occur alongside more serious psychiatric symptoms such as auditory hallucinations, paranoia, or grandiosity. Any time there is a suggestion of psychotic symptoms in a previously healthy person in the late teens or early 20s, a prompt comprehensive psychiatric evaluation is critical. These years are when most chronic psychotic disorders, such as schizophrenia, are likely to emerge. These patients require a thorough evaluation to distinguish these disorders from other illnesses, especially when they occur with substance use. And these patients require specialized care.

If your patient appears to have any psychotic symptoms, it is critical that you help the family find an excellent psychiatrist, or even a clinic that specializes in thought disorders so that he or she may get the best possible care early.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

March often is the time of year when college freshmen truly begin to feel comfortable in their new settings. Many students report feeling excited to get back to campus after the long winter break, and once into their second semester, they feel more comfortable with the independence from family and high school supports. It also is a time for some college freshmen to return home after failing to manage this major transition.

SolStock/Getty Images

Of the latter group, many will have had difficult months of depression, anxiety, or substance use, and most will be suffering from a deep sense of shame after failing to navigate this long-anticipated transition. There are several reasons why some older adolescents fail to manage the transition to college, some more serious than others. Asking detailed questions about their academic challenges, social lives, self-care, and sleep while they were on campus will help you make thoughtful recommendations to your patients and their parents about how they might best get back on track.

Some students will report a great social experience, but academic struggles. They will report some normal ups and downs emotionally, but most of their distress will have been focused on their academic performance. Many 18-year-olds have not had to organize their time and effort around homework without the attention and support of parents and teachers. College often has much bigger classes, with less personal attention. There is a lot of assigned reading, but no regular incremental homework, only a major midterm and final exam, or a substantial paper. For a student who gets anxious about performance, or one with organizational challenges, this can lead to procrastination and poor performance.

Find out details about how they did academically. Did they fail one class or many classes? Did they receive some incompletes in their first semester and then struggle to catch up with them while keeping up with their second semester work? Did they have tutoring or support? Were they unrealistic about their course load? Or did they have their first serious relationship and not spend enough time on homework? Did they spend too much time partying with their new friends and not enough time sleeping and getting their homework done?

It is important to dig deeper if patients report regular or binge drug and alcohol use that interfered with their academic performance, as they may need more substantial substance use disorder treatment. Most students, though, will not have a substance use disorder. Instead, their academic failure could represent something as simple as the need for more academic support and time management support. Many schools have such programs to help students learn how to better manage their time and effort as they take fuller responsibility than they had for it in high school.

For other students, you will learn that their emotional distress preceded their academic troubles. The stress of the transition to college may be enough to trigger an episode of depression or to exacerbate a mood or anxiety disorder that was subclinical or in remission before school started. These students usually will report that sadness, intense anxiety, or loss of interest came early in their semester; perhaps they were even doing well academically when these problems started.

Ask about how their sleep was. Often they had difficulty falling asleep or woke up often at night, unlike most college students, whose sleep is compromised because they stay up late with new friends or because they are hard at work, but could easily sleep at any time.

Find out about their eating habits. Did they lose their appetite? Lose weight? Did they become preoccupied with weight or body image issues and begin restricting their intake? Eating disorders can begin in college when vulnerable students are stressed and have more control over their diet. While weight gain is more common in freshman year, it often is connected to poor stress management skills, and is more often a marker of a student who was struggling academically and then managing stress by overeating.

In the case where the distress came first, it is critical that your patients have a thorough psychiatric evaluation and treatment. It may be possible for them to return to school quickly, but it is most important that they are engaged in effective treatment and in at last partial remission before adding to their stress by attempting to return to school. Often, ambitious students and their parents need to hear this message very clearly from a pediatrician. A rushed return to school may be a set-up for a more protracted and difficult course of illness. For these students, it may be better to have a fresh start in a new semester. Help them (and their parents) to understand that they should use their time off to focus on treatment and good self-care so they might benefit from the many opportunities of college.

For a small minority of college students who do not succeed at college, their social withdrawal, academic deterioration, anxiety, and loss of interest in previous passions may occur alongside more serious psychiatric symptoms such as auditory hallucinations, paranoia, or grandiosity. Any time there is a suggestion of psychotic symptoms in a previously healthy person in the late teens or early 20s, a prompt comprehensive psychiatric evaluation is critical. These years are when most chronic psychotic disorders, such as schizophrenia, are likely to emerge. These patients require a thorough evaluation to distinguish these disorders from other illnesses, especially when they occur with substance use. And these patients require specialized care.

If your patient appears to have any psychotic symptoms, it is critical that you help the family find an excellent psychiatrist, or even a clinic that specializes in thought disorders so that he or she may get the best possible care early.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

March often is the time of year when college freshmen truly begin to feel comfortable in their new settings. Many students report feeling excited to get back to campus after the long winter break, and once into their second semester, they feel more comfortable with the independence from family and high school supports. It also is a time for some college freshmen to return home after failing to manage this major transition.

SolStock/Getty Images

Of the latter group, many will have had difficult months of depression, anxiety, or substance use, and most will be suffering from a deep sense of shame after failing to navigate this long-anticipated transition. There are several reasons why some older adolescents fail to manage the transition to college, some more serious than others. Asking detailed questions about their academic challenges, social lives, self-care, and sleep while they were on campus will help you make thoughtful recommendations to your patients and their parents about how they might best get back on track.

Some students will report a great social experience, but academic struggles. They will report some normal ups and downs emotionally, but most of their distress will have been focused on their academic performance. Many 18-year-olds have not had to organize their time and effort around homework without the attention and support of parents and teachers. College often has much bigger classes, with less personal attention. There is a lot of assigned reading, but no regular incremental homework, only a major midterm and final exam, or a substantial paper. For a student who gets anxious about performance, or one with organizational challenges, this can lead to procrastination and poor performance.

Find out details about how they did academically. Did they fail one class or many classes? Did they receive some incompletes in their first semester and then struggle to catch up with them while keeping up with their second semester work? Did they have tutoring or support? Were they unrealistic about their course load? Or did they have their first serious relationship and not spend enough time on homework? Did they spend too much time partying with their new friends and not enough time sleeping and getting their homework done?

It is important to dig deeper if patients report regular or binge drug and alcohol use that interfered with their academic performance, as they may need more substantial substance use disorder treatment. Most students, though, will not have a substance use disorder. Instead, their academic failure could represent something as simple as the need for more academic support and time management support. Many schools have such programs to help students learn how to better manage their time and effort as they take fuller responsibility than they had for it in high school.

For other students, you will learn that their emotional distress preceded their academic troubles. The stress of the transition to college may be enough to trigger an episode of depression or to exacerbate a mood or anxiety disorder that was subclinical or in remission before school started. These students usually will report that sadness, intense anxiety, or loss of interest came early in their semester; perhaps they were even doing well academically when these problems started.

Ask about how their sleep was. Often they had difficulty falling asleep or woke up often at night, unlike most college students, whose sleep is compromised because they stay up late with new friends or because they are hard at work, but could easily sleep at any time.

Find out about their eating habits. Did they lose their appetite? Lose weight? Did they become preoccupied with weight or body image issues and begin restricting their intake? Eating disorders can begin in college when vulnerable students are stressed and have more control over their diet. While weight gain is more common in freshman year, it often is connected to poor stress management skills, and is more often a marker of a student who was struggling academically and then managing stress by overeating.

In the case where the distress came first, it is critical that your patients have a thorough psychiatric evaluation and treatment. It may be possible for them to return to school quickly, but it is most important that they are engaged in effective treatment and in at last partial remission before adding to their stress by attempting to return to school. Often, ambitious students and their parents need to hear this message very clearly from a pediatrician. A rushed return to school may be a set-up for a more protracted and difficult course of illness. For these students, it may be better to have a fresh start in a new semester. Help them (and their parents) to understand that they should use their time off to focus on treatment and good self-care so they might benefit from the many opportunities of college.

For a small minority of college students who do not succeed at college, their social withdrawal, academic deterioration, anxiety, and loss of interest in previous passions may occur alongside more serious psychiatric symptoms such as auditory hallucinations, paranoia, or grandiosity. Any time there is a suggestion of psychotic symptoms in a previously healthy person in the late teens or early 20s, a prompt comprehensive psychiatric evaluation is critical. These years are when most chronic psychotic disorders, such as schizophrenia, are likely to emerge. These patients require a thorough evaluation to distinguish these disorders from other illnesses, especially when they occur with substance use. And these patients require specialized care.

If your patient appears to have any psychotic symptoms, it is critical that you help the family find an excellent psychiatrist, or even a clinic that specializes in thought disorders so that he or she may get the best possible care early.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.

sdominick/iStock/Getty Images

The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).

“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, the current opioid crisis is largely found among lower-income and majority-white communities,” Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”

Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.

Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.

During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”

Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.

In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).

While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.

“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.

In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).

Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).

“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.

Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.

There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.

sdominick/iStock/Getty Images

The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).

“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, the current opioid crisis is largely found among lower-income and majority-white communities,” Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”

Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.

Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.

During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”

Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.

In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).

While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.

“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.

In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).

Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).

“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.

Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.

There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.

sdominick/iStock/Getty Images

The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).

“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, the current opioid crisis is largely found among lower-income and majority-white communities,” Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”

Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.

Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.

During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”

Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.

In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).

While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.

“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.

In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).

Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).

“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.

Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.

The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.

Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.

“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”

“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.

Study details

Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).

Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).

Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.

Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.

“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.

The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.

Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.

SOURCE: Powles T et al. GUCS 2019, Abstract 543.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.

The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.

Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.

“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”

“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.

Study details

Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).

Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).

Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.

Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.

“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.

The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.

Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.

SOURCE: Powles T et al. GUCS 2019, Abstract 543.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.

The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.

Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.

“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”

“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.

Study details

Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).

Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).

Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.

Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.

“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.

The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.

Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.

SOURCE: Powles T et al. GUCS 2019, Abstract 543.

LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.

Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”

Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”

Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”

In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).

Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.

Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.

More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.

Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.

Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.

The study was funded by a philanthropic grant. The study authors report no relevant disclosures.

SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.

LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.

Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”

Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”

Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”

In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).

Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.

Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.

More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.

Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.

Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.

The study was funded by a philanthropic grant. The study authors report no relevant disclosures.

SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.

LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.

Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”

Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”

Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”

In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).

Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.

Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.

More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.

Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.

Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.

The study was funded by a philanthropic grant. The study authors report no relevant disclosures.

SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.

The mother of three looked tired and little worried. She wasn’t one to bring her kids to the pediatrician’s office with every minor illness, but her youngest had 3 days of fever, runny nose, cough, and little of her normal energy.

DavidWhalen/Thinkstock

The pediatrician entered the room and smiled sympathetically.

“We ran tests for flu and RSV [respiratory syncytial virus] and it’s neither of those so. ...”

“So it’s just a virus that we don’t routinely test for and it’s going to need to run its course,” the mother finished his sentence. She knew the drill.

Before the doctor could leave the room though, the mother had one more question. “You don’t think it could be adenovirus do you?”

Most years, influenza and RSV command center stage, and adenovirus is relegated to the wings. It is not so much lack of disease or morbidity, but rather lack of recognition. Yes, we all learned in medical school that it is a cause of epidemic keratoconjunctivitis, but many adenoviral infections are clinically indistinguishable from infections caused by other viruses. Common symptoms – fever, cough, sore throat, and malaise – overlap with those caused by influenza. Like rhinovirus, adenovirus can cause common cold symptoms. Like RSV, it can cause bronchiolitis. Just like parainfluenza, it can cause croup. It can cause a pertussislike syndrome with prolonged cough, and enteric adenoviruses, especially types 40 and 41, cause gastroenteritis that mimics norovirus or rotavirus infection.

Testing for adenovirus is not readily available or routine in most pediatricians’ offices, and while many hospitals and reference labs offer adenovirus polymerase chain reaction testing as part of a comprehensive respiratory virus panel, the test can be expensive and unlikely to change management in most ambulatory patients. This makes it difficult to count the number of adenoviruses annually.

This winter though, adenovirus was in the news ... repeatedly. In November 2018, CBS News reported that a University of Maryland freshman had died of an adenovirus-related illness. The family of Olivia Paregol told reporters that she was being treated for Crohn’s disease. Immune suppression is one recognized risk factor for more severe adenoviral disease; underlying heart and lung disease are others. Testing at the Centers for Disease Control and Prevention revealed that the student and several others on campus were infected with adenovirus type 7, a strain that has been associated with outbreaks of acute, severe respiratory illness in military recruits. As of Jan. 24, 2019, university officials reported 42 confirmed cases of adenovirus in University of Maryland students, 13 of which were confirmed as adenovirus 7.

Adenovirus type 7 also caused an outbreak at a pediatric long-term care facility in New Jersey late last year. Between Sept. 26 and Nov. 11, 2018, 36 residents and 1 staff member became ill. Eleven individuals died. In an unrelated outbreak at a second pediatric long-term care facility, 17 residents were affected between Oct. 20 and Dec. 10, 2018. Adenovirus 3 was identified and all children recovered.

Depending on your perspective, measures to prevent the spread of adenovirus are elegantly simple, evidence-based, public health intervention or maddeningly little more than common sense. Wash your hands often with soap and water. Avoid touching your eyes, mouth, and nose with unwashed hands. Avoid close contact with people who are sick. The latter is easier if those who are sick stay home. Prior to the start of the most recent academic semester at the University of Maryland, university officials urged students who were sick not to return to campus but to stay at home to rest and recover. Those who fell ill on campus were urged to return home via nonpublic transportation if possible. Those who stayed on campus were advised to stay in their living spaces and clean high-touch surfaces with bleach. Like other nonenveloped viruses, adenovirus is not easily destroyed by many commonly used disinfectants. Under ideal conditions, it can survive on surfaces – remaining infectious – for up to 3 months.

Back at the pediatrician’s office, “We need an adenovirus vaccine,” the mother said as she picked up her child and headed for the door.

There is, in fact, a live oral vaccine that protects against adenovirus types 4 and 7. It is only approved for use in United States military personnel aged 17-50 years and it is given to all recruits as soon as they enter basic training. It works too. Before vaccine was available, up to 80% of recruits became infected during their initial training, half of those developing significant illness and a quarter being hospitalized. When the current vaccine was introduced in 2011, there was a 100-fold decrease in adenovirus-related disease burden (from 5.8 to 0.02 cases per 1,000 person-weeks, P less than .0001). That translates to 1 death, 1,100-2,700 hospitalizations and 13,000 febrile illnesses prevented each year (Clin Infect Dis. 2014 Oct 1. doi: 10.1093/cid/ciu507).

Some experts have suggested that adenovirus vaccine could be useful in civilian populations, too, but I question what the public reception would be. We have safe influenza vaccines that reduce the need for hospitalization and reduce mortality from influenza, but we still can’t convince some people to immunize themselves and their children. In the last 4 years, flu vaccination rates among children have remained just shy of 60% and adult rates are even lower. Collectively, we don’t seem to be ready to relinquish – or at least diminish – the annual suffering that goes with flu. I have to wonder if the same would be true for adenovirus.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

The mother of three looked tired and little worried. She wasn’t one to bring her kids to the pediatrician’s office with every minor illness, but her youngest had 3 days of fever, runny nose, cough, and little of her normal energy.

DavidWhalen/Thinkstock

The pediatrician entered the room and smiled sympathetically.

“We ran tests for flu and RSV [respiratory syncytial virus] and it’s neither of those so. ...”

“So it’s just a virus that we don’t routinely test for and it’s going to need to run its course,” the mother finished his sentence. She knew the drill.

Before the doctor could leave the room though, the mother had one more question. “You don’t think it could be adenovirus do you?”

Most years, influenza and RSV command center stage, and adenovirus is relegated to the wings. It is not so much lack of disease or morbidity, but rather lack of recognition. Yes, we all learned in medical school that it is a cause of epidemic keratoconjunctivitis, but many adenoviral infections are clinically indistinguishable from infections caused by other viruses. Common symptoms – fever, cough, sore throat, and malaise – overlap with those caused by influenza. Like rhinovirus, adenovirus can cause common cold symptoms. Like RSV, it can cause bronchiolitis. Just like parainfluenza, it can cause croup. It can cause a pertussislike syndrome with prolonged cough, and enteric adenoviruses, especially types 40 and 41, cause gastroenteritis that mimics norovirus or rotavirus infection.

Testing for adenovirus is not readily available or routine in most pediatricians’ offices, and while many hospitals and reference labs offer adenovirus polymerase chain reaction testing as part of a comprehensive respiratory virus panel, the test can be expensive and unlikely to change management in most ambulatory patients. This makes it difficult to count the number of adenoviruses annually.

This winter though, adenovirus was in the news ... repeatedly. In November 2018, CBS News reported that a University of Maryland freshman had died of an adenovirus-related illness. The family of Olivia Paregol told reporters that she was being treated for Crohn’s disease. Immune suppression is one recognized risk factor for more severe adenoviral disease; underlying heart and lung disease are others. Testing at the Centers for Disease Control and Prevention revealed that the student and several others on campus were infected with adenovirus type 7, a strain that has been associated with outbreaks of acute, severe respiratory illness in military recruits. As of Jan. 24, 2019, university officials reported 42 confirmed cases of adenovirus in University of Maryland students, 13 of which were confirmed as adenovirus 7.

Adenovirus type 7 also caused an outbreak at a pediatric long-term care facility in New Jersey late last year. Between Sept. 26 and Nov. 11, 2018, 36 residents and 1 staff member became ill. Eleven individuals died. In an unrelated outbreak at a second pediatric long-term care facility, 17 residents were affected between Oct. 20 and Dec. 10, 2018. Adenovirus 3 was identified and all children recovered.

Depending on your perspective, measures to prevent the spread of adenovirus are elegantly simple, evidence-based, public health intervention or maddeningly little more than common sense. Wash your hands often with soap and water. Avoid touching your eyes, mouth, and nose with unwashed hands. Avoid close contact with people who are sick. The latter is easier if those who are sick stay home. Prior to the start of the most recent academic semester at the University of Maryland, university officials urged students who were sick not to return to campus but to stay at home to rest and recover. Those who fell ill on campus were urged to return home via nonpublic transportation if possible. Those who stayed on campus were advised to stay in their living spaces and clean high-touch surfaces with bleach. Like other nonenveloped viruses, adenovirus is not easily destroyed by many commonly used disinfectants. Under ideal conditions, it can survive on surfaces – remaining infectious – for up to 3 months.

Back at the pediatrician’s office, “We need an adenovirus vaccine,” the mother said as she picked up her child and headed for the door.

There is, in fact, a live oral vaccine that protects against adenovirus types 4 and 7. It is only approved for use in United States military personnel aged 17-50 years and it is given to all recruits as soon as they enter basic training. It works too. Before vaccine was available, up to 80% of recruits became infected during their initial training, half of those developing significant illness and a quarter being hospitalized. When the current vaccine was introduced in 2011, there was a 100-fold decrease in adenovirus-related disease burden (from 5.8 to 0.02 cases per 1,000 person-weeks, P less than .0001). That translates to 1 death, 1,100-2,700 hospitalizations and 13,000 febrile illnesses prevented each year (Clin Infect Dis. 2014 Oct 1. doi: 10.1093/cid/ciu507).

Some experts have suggested that adenovirus vaccine could be useful in civilian populations, too, but I question what the public reception would be. We have safe influenza vaccines that reduce the need for hospitalization and reduce mortality from influenza, but we still can’t convince some people to immunize themselves and their children. In the last 4 years, flu vaccination rates among children have remained just shy of 60% and adult rates are even lower. Collectively, we don’t seem to be ready to relinquish – or at least diminish – the annual suffering that goes with flu. I have to wonder if the same would be true for adenovirus.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

The mother of three looked tired and little worried. She wasn’t one to bring her kids to the pediatrician’s office with every minor illness, but her youngest had 3 days of fever, runny nose, cough, and little of her normal energy.

DavidWhalen/Thinkstock

The pediatrician entered the room and smiled sympathetically.

“We ran tests for flu and RSV [respiratory syncytial virus] and it’s neither of those so. ...”

“So it’s just a virus that we don’t routinely test for and it’s going to need to run its course,” the mother finished his sentence. She knew the drill.

Before the doctor could leave the room though, the mother had one more question. “You don’t think it could be adenovirus do you?”

Most years, influenza and RSV command center stage, and adenovirus is relegated to the wings. It is not so much lack of disease or morbidity, but rather lack of recognition. Yes, we all learned in medical school that it is a cause of epidemic keratoconjunctivitis, but many adenoviral infections are clinically indistinguishable from infections caused by other viruses. Common symptoms – fever, cough, sore throat, and malaise – overlap with those caused by influenza. Like rhinovirus, adenovirus can cause common cold symptoms. Like RSV, it can cause bronchiolitis. Just like parainfluenza, it can cause croup. It can cause a pertussislike syndrome with prolonged cough, and enteric adenoviruses, especially types 40 and 41, cause gastroenteritis that mimics norovirus or rotavirus infection.

Testing for adenovirus is not readily available or routine in most pediatricians’ offices, and while many hospitals and reference labs offer adenovirus polymerase chain reaction testing as part of a comprehensive respiratory virus panel, the test can be expensive and unlikely to change management in most ambulatory patients. This makes it difficult to count the number of adenoviruses annually.

This winter though, adenovirus was in the news ... repeatedly. In November 2018, CBS News reported that a University of Maryland freshman had died of an adenovirus-related illness. The family of Olivia Paregol told reporters that she was being treated for Crohn’s disease. Immune suppression is one recognized risk factor for more severe adenoviral disease; underlying heart and lung disease are others. Testing at the Centers for Disease Control and Prevention revealed that the student and several others on campus were infected with adenovirus type 7, a strain that has been associated with outbreaks of acute, severe respiratory illness in military recruits. As of Jan. 24, 2019, university officials reported 42 confirmed cases of adenovirus in University of Maryland students, 13 of which were confirmed as adenovirus 7.

Adenovirus type 7 also caused an outbreak at a pediatric long-term care facility in New Jersey late last year. Between Sept. 26 and Nov. 11, 2018, 36 residents and 1 staff member became ill. Eleven individuals died. In an unrelated outbreak at a second pediatric long-term care facility, 17 residents were affected between Oct. 20 and Dec. 10, 2018. Adenovirus 3 was identified and all children recovered.

Depending on your perspective, measures to prevent the spread of adenovirus are elegantly simple, evidence-based, public health intervention or maddeningly little more than common sense. Wash your hands often with soap and water. Avoid touching your eyes, mouth, and nose with unwashed hands. Avoid close contact with people who are sick. The latter is easier if those who are sick stay home. Prior to the start of the most recent academic semester at the University of Maryland, university officials urged students who were sick not to return to campus but to stay at home to rest and recover. Those who fell ill on campus were urged to return home via nonpublic transportation if possible. Those who stayed on campus were advised to stay in their living spaces and clean high-touch surfaces with bleach. Like other nonenveloped viruses, adenovirus is not easily destroyed by many commonly used disinfectants. Under ideal conditions, it can survive on surfaces – remaining infectious – for up to 3 months.

Back at the pediatrician’s office, “We need an adenovirus vaccine,” the mother said as she picked up her child and headed for the door.

There is, in fact, a live oral vaccine that protects against adenovirus types 4 and 7. It is only approved for use in United States military personnel aged 17-50 years and it is given to all recruits as soon as they enter basic training. It works too. Before vaccine was available, up to 80% of recruits became infected during their initial training, half of those developing significant illness and a quarter being hospitalized. When the current vaccine was introduced in 2011, there was a 100-fold decrease in adenovirus-related disease burden (from 5.8 to 0.02 cases per 1,000 person-weeks, P less than .0001). That translates to 1 death, 1,100-2,700 hospitalizations and 13,000 febrile illnesses prevented each year (Clin Infect Dis. 2014 Oct 1. doi: 10.1093/cid/ciu507).

Some experts have suggested that adenovirus vaccine could be useful in civilian populations, too, but I question what the public reception would be. We have safe influenza vaccines that reduce the need for hospitalization and reduce mortality from influenza, but we still can’t convince some people to immunize themselves and their children. In the last 4 years, flu vaccination rates among children have remained just shy of 60% and adult rates are even lower. Collectively, we don’t seem to be ready to relinquish – or at least diminish – the annual suffering that goes with flu. I have to wonder if the same would be true for adenovirus.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

Are residents generally prepared for fellowship interviews? Applications to the Fellowship Match through the National Residency Matching Program (NRMP) Specialties Matching Service (SMS) are at an all-time high, but there is limited data regarding the preparedness of residents who go through the fellowship interview process, said Kelvin Wong, MD, a coauthor of research describing a new approach to fellowship interview preparation, which may be generalizable to hospitalists in applying for other positions.

“Applicants receive little to no feedback after their interviews and are thus likely to repeat the same mistakes throughout the process. Verbal feedback from our own fellowship directors indicated that residents as a whole are unprepared to interview,” according to an abstract written by Dr. Wong and his colleagues.

Dr. Wong wanted to investigate the effects of a standardized fellowship interview preparation course on resident preparedness. He and his coauthors developed a formal preparation course for the applicants in the summer of 2017.

Precourse surveys showed that only 17.65% of residents felt prepared to go on interviews; postcourse surveys showed a rise in this number to 82.35%. Immediately after their mock interview, only 27.78% of residents rated their overall interview skills as “very good” or “excellent,” whereas 87.5% of interviewers and 70.59% of observers rated their skills to be “very good” or “excellent.”

A final survey will be given to the applicants and the fellowship program directors once the applicants have completed all of their actual interviews.

“This demonstrates the potential positive impact that mock interviews and standardized interview preparation courses can have, which may be generalizable to hospitalists applying for other positions,” Dr. Wong said. “Specifically for teaching hospitalists in teaching hospitals, the institution of such fellowship interview preparation courses may improve resident preparedness for the fellowship application process.”
 

Reference

1. Wong K et al. A novel approach to improve fellowship interview skills [abstract]. https://www.shmabstracts.com/abstract/a-novel-approach-to-improve-fellowship-interview-skills/.

Are residents generally prepared for fellowship interviews? Applications to the Fellowship Match through the National Residency Matching Program (NRMP) Specialties Matching Service (SMS) are at an all-time high, but there is limited data regarding the preparedness of residents who go through the fellowship interview process, said Kelvin Wong, MD, a coauthor of research describing a new approach to fellowship interview preparation, which may be generalizable to hospitalists in applying for other positions.

“Applicants receive little to no feedback after their interviews and are thus likely to repeat the same mistakes throughout the process. Verbal feedback from our own fellowship directors indicated that residents as a whole are unprepared to interview,” according to an abstract written by Dr. Wong and his colleagues.

Dr. Wong wanted to investigate the effects of a standardized fellowship interview preparation course on resident preparedness. He and his coauthors developed a formal preparation course for the applicants in the summer of 2017.

Precourse surveys showed that only 17.65% of residents felt prepared to go on interviews; postcourse surveys showed a rise in this number to 82.35%. Immediately after their mock interview, only 27.78% of residents rated their overall interview skills as “very good” or “excellent,” whereas 87.5% of interviewers and 70.59% of observers rated their skills to be “very good” or “excellent.”

A final survey will be given to the applicants and the fellowship program directors once the applicants have completed all of their actual interviews.

“This demonstrates the potential positive impact that mock interviews and standardized interview preparation courses can have, which may be generalizable to hospitalists applying for other positions,” Dr. Wong said. “Specifically for teaching hospitalists in teaching hospitals, the institution of such fellowship interview preparation courses may improve resident preparedness for the fellowship application process.”
 

Reference

1. Wong K et al. A novel approach to improve fellowship interview skills [abstract]. https://www.shmabstracts.com/abstract/a-novel-approach-to-improve-fellowship-interview-skills/.

Are residents generally prepared for fellowship interviews? Applications to the Fellowship Match through the National Residency Matching Program (NRMP) Specialties Matching Service (SMS) are at an all-time high, but there is limited data regarding the preparedness of residents who go through the fellowship interview process, said Kelvin Wong, MD, a coauthor of research describing a new approach to fellowship interview preparation, which may be generalizable to hospitalists in applying for other positions.

“Applicants receive little to no feedback after their interviews and are thus likely to repeat the same mistakes throughout the process. Verbal feedback from our own fellowship directors indicated that residents as a whole are unprepared to interview,” according to an abstract written by Dr. Wong and his colleagues.

Dr. Wong wanted to investigate the effects of a standardized fellowship interview preparation course on resident preparedness. He and his coauthors developed a formal preparation course for the applicants in the summer of 2017.

Precourse surveys showed that only 17.65% of residents felt prepared to go on interviews; postcourse surveys showed a rise in this number to 82.35%. Immediately after their mock interview, only 27.78% of residents rated their overall interview skills as “very good” or “excellent,” whereas 87.5% of interviewers and 70.59% of observers rated their skills to be “very good” or “excellent.”

A final survey will be given to the applicants and the fellowship program directors once the applicants have completed all of their actual interviews.

“This demonstrates the potential positive impact that mock interviews and standardized interview preparation courses can have, which may be generalizable to hospitalists applying for other positions,” Dr. Wong said. “Specifically for teaching hospitalists in teaching hospitals, the institution of such fellowship interview preparation courses may improve resident preparedness for the fellowship application process.”
 

Reference

1. Wong K et al. A novel approach to improve fellowship interview skills [abstract]. https://www.shmabstracts.com/abstract/a-novel-approach-to-improve-fellowship-interview-skills/.

SAN FRANCISCO – Men with metastatic castrate-resistant prostate cancer (mCRPC) who have exhausted conventional treatment options have very good outcomes when treated with the novel targeted radioligand lutetium-177 PSMA-617 (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.

LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.

With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.

“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.

“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”

The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”

“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
 

Study details

Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.

The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.

The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.

Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.

For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).

Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.

Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
 

SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
 

SAN FRANCISCO – Men with metastatic castrate-resistant prostate cancer (mCRPC) who have exhausted conventional treatment options have very good outcomes when treated with the novel targeted radioligand lutetium-177 PSMA-617 (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.

LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.

With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.

“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.

“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”

The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”

“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
 

Study details

Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.

The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.

The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.

Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.

For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).

Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.

Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
 

SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
 

SAN FRANCISCO – Men with metastatic castrate-resistant prostate cancer (mCRPC) who have exhausted conventional treatment options have very good outcomes when treated with the novel targeted radioligand lutetium-177 PSMA-617 (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.

LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.

With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.

“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.

“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”

The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”

“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
 

Study details

Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.

The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.

The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.

Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.

For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).

Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.

Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
 

SOURCE: Hofman M et al. GUCS 2019, Abstract 228.