Men's Health

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

Men who undergo MRI of the prostate around the time of a low-risk prostate cancer diagnosis are nearly twice as likely to be managed with active surveillance as are men who do not get MRI, investigators found.

roobcio/Thinkstock.com

The findings suggest that MRI at the time of diagnosis can enhance patient and physician confidence in the decision to choose active surveillance (AS) over immediate surgery or radiation therapy in men with low-risk disease, according to Michael S. Leapman, MD, and his colleagues from Yale University, New Haven, Conn.

“Despite initial high costs associated with obtaining and interpreting MRI studies of the prostate, economic modeling studies imply that MRI would be cost effective if it resulted in increased utilization of AS for low- and very-low-risk PCa [prostate cancer]. The association identified in our study between MRI use and initial observation may serve as an informative basis for examining strategies to improve the quality of PCa care with the anticipated growing use of this technology,” they wrote in Urology.

Although active surveillance is increasingly accepted as an initial management strategy for patients with low-risk (Gleason score 6 or less) localized prostate cancer, the majority of patients with low-risk disease still receive definitive treatment.

“Although longitudinal studies support the safety of AS, uncertainty about the possibility of underestimating an indvidual’s risk of harboring aggressive disease remains a strong motivator to treat,” Dr. Leapman and his associates noted.

To see whether MRI of the prostate may have an effect on the use of active surveillance in men with low-risk disease, the investigators reviewed records from the Surveillance, Epidemiology and End Results (SEER) Medicare database to identify men diagnosed with low-risk prostate cancer during 2010-2013.

They looked at the association between MRI and patient management (ascertained by claims) and evaluated clinical and demographic factors associated with the receipt of MRI.

They identified 8,144 patients with low-risk prostate cancer during the study period, of whom 495 (6.1%) had undergone MRI scans. They found that the use of MRI in patients with low-risk cancer increased from 3.4% in 2010 to 10.5% in 2013.

MRI was performed significantly more frequently among 3,060 patients who were managed with observation, with 265 (8.7%) receiving scans, compared with 230 (4.5%) of the 5,084 patients who underwent treatment within a year of diagnosis.

In multivariable analysis that controlled for demographics, factors significantly associated with increased likelihood of undergoing observation versus definitive therapy included MRI, white vs. nonwhite race, later years of diagnosis, higher income status (by ZIP code), unmarried vs. married, treatment region (more common in the West and Midwest versus Northeast or South), and in referral regions with higher population density of urologists.

In a propensity score–matched analysis designed to smooth out potential confounders, the investigators found that receipt of MRI around the time of diagnosis was associated with a significantly higher likelihood of active surveillance, with an odds ratio of 1.90 (95% confidence interval, 1.56-2.32).

“Efforts to facilitate observational approaches for low-risk PCa are highly valuable to improving the quality of cancer care. Because the use of prostate MRI has grown, and is likely to continue expanding, the cost-effectiveness of MRI-driven pathways are increasingly relevant to the sustainability of the practice,” the authors wrote.

SOURCE: Leapman MS et al. Urology. 2018 Aug 11. doi: 10.1016/j.urology.2018.07.041.

Men who undergo MRI of the prostate around the time of a low-risk prostate cancer diagnosis are nearly twice as likely to be managed with active surveillance as are men who do not get MRI, investigators found.

roobcio/Thinkstock.com

The findings suggest that MRI at the time of diagnosis can enhance patient and physician confidence in the decision to choose active surveillance (AS) over immediate surgery or radiation therapy in men with low-risk disease, according to Michael S. Leapman, MD, and his colleagues from Yale University, New Haven, Conn.

“Despite initial high costs associated with obtaining and interpreting MRI studies of the prostate, economic modeling studies imply that MRI would be cost effective if it resulted in increased utilization of AS for low- and very-low-risk PCa [prostate cancer]. The association identified in our study between MRI use and initial observation may serve as an informative basis for examining strategies to improve the quality of PCa care with the anticipated growing use of this technology,” they wrote in Urology.

Although active surveillance is increasingly accepted as an initial management strategy for patients with low-risk (Gleason score 6 or less) localized prostate cancer, the majority of patients with low-risk disease still receive definitive treatment.

“Although longitudinal studies support the safety of AS, uncertainty about the possibility of underestimating an indvidual’s risk of harboring aggressive disease remains a strong motivator to treat,” Dr. Leapman and his associates noted.

To see whether MRI of the prostate may have an effect on the use of active surveillance in men with low-risk disease, the investigators reviewed records from the Surveillance, Epidemiology and End Results (SEER) Medicare database to identify men diagnosed with low-risk prostate cancer during 2010-2013.

They looked at the association between MRI and patient management (ascertained by claims) and evaluated clinical and demographic factors associated with the receipt of MRI.

They identified 8,144 patients with low-risk prostate cancer during the study period, of whom 495 (6.1%) had undergone MRI scans. They found that the use of MRI in patients with low-risk cancer increased from 3.4% in 2010 to 10.5% in 2013.

MRI was performed significantly more frequently among 3,060 patients who were managed with observation, with 265 (8.7%) receiving scans, compared with 230 (4.5%) of the 5,084 patients who underwent treatment within a year of diagnosis.

In multivariable analysis that controlled for demographics, factors significantly associated with increased likelihood of undergoing observation versus definitive therapy included MRI, white vs. nonwhite race, later years of diagnosis, higher income status (by ZIP code), unmarried vs. married, treatment region (more common in the West and Midwest versus Northeast or South), and in referral regions with higher population density of urologists.

In a propensity score–matched analysis designed to smooth out potential confounders, the investigators found that receipt of MRI around the time of diagnosis was associated with a significantly higher likelihood of active surveillance, with an odds ratio of 1.90 (95% confidence interval, 1.56-2.32).

“Efforts to facilitate observational approaches for low-risk PCa are highly valuable to improving the quality of cancer care. Because the use of prostate MRI has grown, and is likely to continue expanding, the cost-effectiveness of MRI-driven pathways are increasingly relevant to the sustainability of the practice,” the authors wrote.

SOURCE: Leapman MS et al. Urology. 2018 Aug 11. doi: 10.1016/j.urology.2018.07.041.

Men who undergo MRI of the prostate around the time of a low-risk prostate cancer diagnosis are nearly twice as likely to be managed with active surveillance as are men who do not get MRI, investigators found.

roobcio/Thinkstock.com

The findings suggest that MRI at the time of diagnosis can enhance patient and physician confidence in the decision to choose active surveillance (AS) over immediate surgery or radiation therapy in men with low-risk disease, according to Michael S. Leapman, MD, and his colleagues from Yale University, New Haven, Conn.

“Despite initial high costs associated with obtaining and interpreting MRI studies of the prostate, economic modeling studies imply that MRI would be cost effective if it resulted in increased utilization of AS for low- and very-low-risk PCa [prostate cancer]. The association identified in our study between MRI use and initial observation may serve as an informative basis for examining strategies to improve the quality of PCa care with the anticipated growing use of this technology,” they wrote in Urology.

Although active surveillance is increasingly accepted as an initial management strategy for patients with low-risk (Gleason score 6 or less) localized prostate cancer, the majority of patients with low-risk disease still receive definitive treatment.

“Although longitudinal studies support the safety of AS, uncertainty about the possibility of underestimating an indvidual’s risk of harboring aggressive disease remains a strong motivator to treat,” Dr. Leapman and his associates noted.

To see whether MRI of the prostate may have an effect on the use of active surveillance in men with low-risk disease, the investigators reviewed records from the Surveillance, Epidemiology and End Results (SEER) Medicare database to identify men diagnosed with low-risk prostate cancer during 2010-2013.

They looked at the association between MRI and patient management (ascertained by claims) and evaluated clinical and demographic factors associated with the receipt of MRI.

They identified 8,144 patients with low-risk prostate cancer during the study period, of whom 495 (6.1%) had undergone MRI scans. They found that the use of MRI in patients with low-risk cancer increased from 3.4% in 2010 to 10.5% in 2013.

MRI was performed significantly more frequently among 3,060 patients who were managed with observation, with 265 (8.7%) receiving scans, compared with 230 (4.5%) of the 5,084 patients who underwent treatment within a year of diagnosis.

In multivariable analysis that controlled for demographics, factors significantly associated with increased likelihood of undergoing observation versus definitive therapy included MRI, white vs. nonwhite race, later years of diagnosis, higher income status (by ZIP code), unmarried vs. married, treatment region (more common in the West and Midwest versus Northeast or South), and in referral regions with higher population density of urologists.

In a propensity score–matched analysis designed to smooth out potential confounders, the investigators found that receipt of MRI around the time of diagnosis was associated with a significantly higher likelihood of active surveillance, with an odds ratio of 1.90 (95% confidence interval, 1.56-2.32).

“Efforts to facilitate observational approaches for low-risk PCa are highly valuable to improving the quality of cancer care. Because the use of prostate MRI has grown, and is likely to continue expanding, the cost-effectiveness of MRI-driven pathways are increasingly relevant to the sustainability of the practice,” the authors wrote.

SOURCE: Leapman MS et al. Urology. 2018 Aug 11. doi: 10.1016/j.urology.2018.07.041.

An 88-year-old man with a 1-day history of fever and altered mental status was transferred to the emergency department. He had been receiving conservative management for low-risk localized prostate cancer but had no previous cardiovascular or gastrointestinal problems.

Based on these findings, the diagnosis was Fournier gangrene. Despite aggressive treatment, the patient’s condition deteriorated rapidly, and he died 2 hours after admission.

FOURNIER GANGRENE: NECROTIZING FASCIITIS OF THE PERINEUM

Fournier gangrene is a rare but rapidly progressive necrotizing fasciitis of the perineum with a high death rate.

Predisposing factors for Fournier gangrene include older age, diabetes mellitus, morbid obesity, cardiovascular disorders, chronic alcoholism, long-term corticosteroid treatment, malignancy, and human immunodeficiency virus infection.^1,2 Urethral obstruction, instrumentation, urinary extravasation, and trauma have also been associated with this condition.³

In general, organisms from the urinary tract spread along the fascial planes to involve the penis and scrotum.

The differential diagnosis of Fournier gangrene includes scrotal and perineal disorders, as well as intra-abdominal disorders such as cellulitis, abscess, strangulated hernia, pyoderma gangrenosum, allergic vasculitis, vascular occlusion syndromes, and warfarin necrosis.

Delay in the diagnosis of Fournier gangrene leads to an extremely high death rate due to rapid progression of the disease, leading to sepsis, multiple organ failure, and disseminated intravascular coagulation. Immediate diagnosis and appropriate treatment such as broad-spectrum antibiotics and extensive surgical debridement reduce morbidity and control the infection. Antibiotics for methicillin-resistant Staphylococcus aureus should be considered if there is a history of or risk factors for this organism.⁴

Necrotizing fasciitis, including Fournier gangrene, is a common indication for intravenous immunoglobulin, and this treatment has been reported to be effective in a few cases. However, a double-blind, placebo-controlled trial that evaluated the benefit of this treatment was terminated early due to slow patient recruitment.⁵

A delay of even a few hours from suspicion of Fournier gangrene to surgical debridement significantly increases the risk of death.⁶ Thus, when it is suspected, immediate surgical intervention may be necessary to confirm the diagnosis and to treat it. The usual combination of antibiotic therapy for Fournier gangrene includes penicillin for the streptococcal species, a third-generation cephalosporin with or without an aminoglycoside for the gram-negative organisms, and metronidazole for anaerobic bacteria.

An 88-year-old man with a 1-day history of fever and altered mental status was transferred to the emergency department. He had been receiving conservative management for low-risk localized prostate cancer but had no previous cardiovascular or gastrointestinal problems.

Based on these findings, the diagnosis was Fournier gangrene. Despite aggressive treatment, the patient’s condition deteriorated rapidly, and he died 2 hours after admission.

FOURNIER GANGRENE: NECROTIZING FASCIITIS OF THE PERINEUM

Fournier gangrene is a rare but rapidly progressive necrotizing fasciitis of the perineum with a high death rate.

Predisposing factors for Fournier gangrene include older age, diabetes mellitus, morbid obesity, cardiovascular disorders, chronic alcoholism, long-term corticosteroid treatment, malignancy, and human immunodeficiency virus infection.^1,2 Urethral obstruction, instrumentation, urinary extravasation, and trauma have also been associated with this condition.³

In general, organisms from the urinary tract spread along the fascial planes to involve the penis and scrotum.

The differential diagnosis of Fournier gangrene includes scrotal and perineal disorders, as well as intra-abdominal disorders such as cellulitis, abscess, strangulated hernia, pyoderma gangrenosum, allergic vasculitis, vascular occlusion syndromes, and warfarin necrosis.

Delay in the diagnosis of Fournier gangrene leads to an extremely high death rate due to rapid progression of the disease, leading to sepsis, multiple organ failure, and disseminated intravascular coagulation. Immediate diagnosis and appropriate treatment such as broad-spectrum antibiotics and extensive surgical debridement reduce morbidity and control the infection. Antibiotics for methicillin-resistant Staphylococcus aureus should be considered if there is a history of or risk factors for this organism.⁴

Necrotizing fasciitis, including Fournier gangrene, is a common indication for intravenous immunoglobulin, and this treatment has been reported to be effective in a few cases. However, a double-blind, placebo-controlled trial that evaluated the benefit of this treatment was terminated early due to slow patient recruitment.⁵

A delay of even a few hours from suspicion of Fournier gangrene to surgical debridement significantly increases the risk of death.⁶ Thus, when it is suspected, immediate surgical intervention may be necessary to confirm the diagnosis and to treat it. The usual combination of antibiotic therapy for Fournier gangrene includes penicillin for the streptococcal species, a third-generation cephalosporin with or without an aminoglycoside for the gram-negative organisms, and metronidazole for anaerobic bacteria.

An 88-year-old man with a 1-day history of fever and altered mental status was transferred to the emergency department. He had been receiving conservative management for low-risk localized prostate cancer but had no previous cardiovascular or gastrointestinal problems.

Based on these findings, the diagnosis was Fournier gangrene. Despite aggressive treatment, the patient’s condition deteriorated rapidly, and he died 2 hours after admission.

FOURNIER GANGRENE: NECROTIZING FASCIITIS OF THE PERINEUM

Fournier gangrene is a rare but rapidly progressive necrotizing fasciitis of the perineum with a high death rate.

Predisposing factors for Fournier gangrene include older age, diabetes mellitus, morbid obesity, cardiovascular disorders, chronic alcoholism, long-term corticosteroid treatment, malignancy, and human immunodeficiency virus infection.^1,2 Urethral obstruction, instrumentation, urinary extravasation, and trauma have also been associated with this condition.³

In general, organisms from the urinary tract spread along the fascial planes to involve the penis and scrotum.

The differential diagnosis of Fournier gangrene includes scrotal and perineal disorders, as well as intra-abdominal disorders such as cellulitis, abscess, strangulated hernia, pyoderma gangrenosum, allergic vasculitis, vascular occlusion syndromes, and warfarin necrosis.

Delay in the diagnosis of Fournier gangrene leads to an extremely high death rate due to rapid progression of the disease, leading to sepsis, multiple organ failure, and disseminated intravascular coagulation. Immediate diagnosis and appropriate treatment such as broad-spectrum antibiotics and extensive surgical debridement reduce morbidity and control the infection. Antibiotics for methicillin-resistant Staphylococcus aureus should be considered if there is a history of or risk factors for this organism.⁴

Necrotizing fasciitis, including Fournier gangrene, is a common indication for intravenous immunoglobulin, and this treatment has been reported to be effective in a few cases. However, a double-blind, placebo-controlled trial that evaluated the benefit of this treatment was terminated early due to slow patient recruitment.⁵

A delay of even a few hours from suspicion of Fournier gangrene to surgical debridement significantly increases the risk of death.⁶ Thus, when it is suspected, immediate surgical intervention may be necessary to confirm the diagnosis and to treat it. The usual combination of antibiotic therapy for Fournier gangrene includes penicillin for the streptococcal species, a third-generation cephalosporin with or without an aminoglycoside for the gram-negative organisms, and metronidazole for anaerobic bacteria.

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

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

[email protected]

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

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

[email protected]

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

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

[email protected]

A 51-year-old man with type 2 diabetes was referred to our hospital because of liver dysfunction and nonpruritic exanthema, with papulosquamous, scaly, papular and macular lesions on his trunk and extremities, including his palms (Figure 1) and soles. Also noted were tiny grayish mucus patches on the oral mucosa. Axillary and inguinal superficial lymph nodes were palpable.

Laboratory testing revealed elevated serum levels of markers of liver disease, ie:

• Total bilirubin 9.8 mg/dL (reference range 0.2–1.3)
• Direct bilirubin 8.0 mg/dL (< 0.2)
• Aspartate aminotransferase 57 IU/L (13–35)
• Alanine aminotransferase 90 IU/L (10–54)
• Alkaline phosphatase 4,446 IU/L (36–108).

Possible causes of liver dysfunction such as legal and illicit drugs, alcohol abuse, obstructive biliary tract or liver disease, viral hepatitis, and primary biliary cirrhosis were ruled out by history, serologic testing, abdominal ultrasonography, and computed tomography.

Secondary syphilis was suspected in view of the characteristic distribution of exanthema involving the trunk and extremities, especially the palms and soles. On questioning, the patient admitted to having had unprotected sex with a female sex worker, which also raised the probability of syphilis infection.

The rapid plasma reagin test was positive at a titer of 1:16, and the Treponema pallidum agglutination test was positive at a signal-to-cutoff ratio of 27.02. Antibody testing for human immunodeficiency virus (HIV) was negative.

The patient was started on penicillin G, but 4 hours later, he developed a fever with a temperature of 100.2°F (37.9°C), which was assumed to be a Jarisch-Herxheimer reaction. The fever resolved by the next morning without further treatment.

His course was otherwise uneventful. The exanthema resolved within 3 months, and his liver function returned to normal. Five months later, the rapid plasma reagin test was repeated on an outpatient basis, and the result was normal.

SYPHILIS IS NOT A DISEASE OF THE PAST

Syphilis is caused by T pallidum and is mainly transmitted by sexual contact.¹

The incidence of syphilis has substantially increased in recent years in Japan^2,3 and worldwide.⁴ The typical patient is a young man who has sex with men, is infected with HIV, and has a history of syphilis infection.³ However, the rapid increase in syphilis infections in Japan in recent years is largely because of an increase in heterosexual transmission.³

Infectious in its early stages

Syphilis is potentially infectious in its early (primary, secondary, and early latent) stages.^1,5 The secondary stage generally begins 6 to 8 weeks after the primary infection¹ and presents with diverse symptoms, including arthralgia, condylomata lata, generalized lymphaden­opathy, maculopapular and papulosquamous exanthema, myalgia, and pharyngitis.¹

Liver dysfunction in secondary syphilis

Liver dysfunction is common in secondary syphilis, occurring in 25% to 50% of cases.⁵ The liver enzyme pattern in most cases is a disproportionate increase in the alkaline phosphatase level compared with modest elevations of aminotransferases and bilirubin.^2,5 However, some cases may show predominant hepatocellular damage (with prominent elevations in aminotransferase levels), and others may present with severe cholestasis (with prominent elevations in alkaline phosphatase and bilirubin) or even fulminant hepatic failure.^2,5

The diagnostic criteria for syphilitic hepatitis are abnormal liver enzyme levels, serologic evidence of syphilis in conjunction with acute clinical presentation of secondary syphilis, exclusion of alternative causes of liver dysfunction, and prompt recovery of liver function after antimicrobial therapy.^2,5

Pathogenic mechanisms in syphilitic hepatitis include direct portal venous inoculation and immune complex-mediated disease.² However, direct hepatotoxicity of the microorganism seems unlikely, as spirochetes are rarely detected in liver specimens.^2,5

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction is an acute febrile illness during the first 24 hours of antimicrobial treatment.^1,6 It is assumed to be due to lysis of large numbers of spirochetes, releasing lipopolysaccharides (endotoxins) that further incite the release of a range of cytokines, resulting in symptoms such as fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.^6,7

The frequency of Jarisch-Herxheimer reaction in syphilis and other spirochetal infections has varied widely in different reports.⁸ It is common in primary and secondary syphilis but usually does not occur in latent syphilis.⁶

Consider the diagnosis

Physicians should consider secondary syphilis in patients who present with characteristic generalized reddish macules and papules with papulosquamous lesions, including on the palms and soles as in our patient, and also in patients who have had unprotected sexual contact. Syphilis is not a disease of the past.

Acknowledgment: The authors thank Dr. Joel Branch, Shonan Kamakura General Hospital, Japan, for his editorial assistance.

A 51-year-old man with type 2 diabetes was referred to our hospital because of liver dysfunction and nonpruritic exanthema, with papulosquamous, scaly, papular and macular lesions on his trunk and extremities, including his palms (Figure 1) and soles. Also noted were tiny grayish mucus patches on the oral mucosa. Axillary and inguinal superficial lymph nodes were palpable.

Laboratory testing revealed elevated serum levels of markers of liver disease, ie:

• Total bilirubin 9.8 mg/dL (reference range 0.2–1.3)
• Direct bilirubin 8.0 mg/dL (< 0.2)
• Aspartate aminotransferase 57 IU/L (13–35)
• Alanine aminotransferase 90 IU/L (10–54)
• Alkaline phosphatase 4,446 IU/L (36–108).

Possible causes of liver dysfunction such as legal and illicit drugs, alcohol abuse, obstructive biliary tract or liver disease, viral hepatitis, and primary biliary cirrhosis were ruled out by history, serologic testing, abdominal ultrasonography, and computed tomography.

Secondary syphilis was suspected in view of the characteristic distribution of exanthema involving the trunk and extremities, especially the palms and soles. On questioning, the patient admitted to having had unprotected sex with a female sex worker, which also raised the probability of syphilis infection.

The rapid plasma reagin test was positive at a titer of 1:16, and the Treponema pallidum agglutination test was positive at a signal-to-cutoff ratio of 27.02. Antibody testing for human immunodeficiency virus (HIV) was negative.

The patient was started on penicillin G, but 4 hours later, he developed a fever with a temperature of 100.2°F (37.9°C), which was assumed to be a Jarisch-Herxheimer reaction. The fever resolved by the next morning without further treatment.

His course was otherwise uneventful. The exanthema resolved within 3 months, and his liver function returned to normal. Five months later, the rapid plasma reagin test was repeated on an outpatient basis, and the result was normal.

SYPHILIS IS NOT A DISEASE OF THE PAST

Syphilis is caused by T pallidum and is mainly transmitted by sexual contact.¹

The incidence of syphilis has substantially increased in recent years in Japan^2,3 and worldwide.⁴ The typical patient is a young man who has sex with men, is infected with HIV, and has a history of syphilis infection.³ However, the rapid increase in syphilis infections in Japan in recent years is largely because of an increase in heterosexual transmission.³

Infectious in its early stages

Syphilis is potentially infectious in its early (primary, secondary, and early latent) stages.^1,5 The secondary stage generally begins 6 to 8 weeks after the primary infection¹ and presents with diverse symptoms, including arthralgia, condylomata lata, generalized lymphaden­opathy, maculopapular and papulosquamous exanthema, myalgia, and pharyngitis.¹

Liver dysfunction in secondary syphilis

Liver dysfunction is common in secondary syphilis, occurring in 25% to 50% of cases.⁵ The liver enzyme pattern in most cases is a disproportionate increase in the alkaline phosphatase level compared with modest elevations of aminotransferases and bilirubin.^2,5 However, some cases may show predominant hepatocellular damage (with prominent elevations in aminotransferase levels), and others may present with severe cholestasis (with prominent elevations in alkaline phosphatase and bilirubin) or even fulminant hepatic failure.^2,5

The diagnostic criteria for syphilitic hepatitis are abnormal liver enzyme levels, serologic evidence of syphilis in conjunction with acute clinical presentation of secondary syphilis, exclusion of alternative causes of liver dysfunction, and prompt recovery of liver function after antimicrobial therapy.^2,5

Pathogenic mechanisms in syphilitic hepatitis include direct portal venous inoculation and immune complex-mediated disease.² However, direct hepatotoxicity of the microorganism seems unlikely, as spirochetes are rarely detected in liver specimens.^2,5

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction is an acute febrile illness during the first 24 hours of antimicrobial treatment.^1,6 It is assumed to be due to lysis of large numbers of spirochetes, releasing lipopolysaccharides (endotoxins) that further incite the release of a range of cytokines, resulting in symptoms such as fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.^6,7

The frequency of Jarisch-Herxheimer reaction in syphilis and other spirochetal infections has varied widely in different reports.⁸ It is common in primary and secondary syphilis but usually does not occur in latent syphilis.⁶

Consider the diagnosis

Physicians should consider secondary syphilis in patients who present with characteristic generalized reddish macules and papules with papulosquamous lesions, including on the palms and soles as in our patient, and also in patients who have had unprotected sexual contact. Syphilis is not a disease of the past.

Acknowledgment: The authors thank Dr. Joel Branch, Shonan Kamakura General Hospital, Japan, for his editorial assistance.

A 51-year-old man with type 2 diabetes was referred to our hospital because of liver dysfunction and nonpruritic exanthema, with papulosquamous, scaly, papular and macular lesions on his trunk and extremities, including his palms (Figure 1) and soles. Also noted were tiny grayish mucus patches on the oral mucosa. Axillary and inguinal superficial lymph nodes were palpable.

Laboratory testing revealed elevated serum levels of markers of liver disease, ie:

• Total bilirubin 9.8 mg/dL (reference range 0.2–1.3)
• Direct bilirubin 8.0 mg/dL (< 0.2)
• Aspartate aminotransferase 57 IU/L (13–35)
• Alanine aminotransferase 90 IU/L (10–54)
• Alkaline phosphatase 4,446 IU/L (36–108).

Possible causes of liver dysfunction such as legal and illicit drugs, alcohol abuse, obstructive biliary tract or liver disease, viral hepatitis, and primary biliary cirrhosis were ruled out by history, serologic testing, abdominal ultrasonography, and computed tomography.

Secondary syphilis was suspected in view of the characteristic distribution of exanthema involving the trunk and extremities, especially the palms and soles. On questioning, the patient admitted to having had unprotected sex with a female sex worker, which also raised the probability of syphilis infection.

The rapid plasma reagin test was positive at a titer of 1:16, and the Treponema pallidum agglutination test was positive at a signal-to-cutoff ratio of 27.02. Antibody testing for human immunodeficiency virus (HIV) was negative.

The patient was started on penicillin G, but 4 hours later, he developed a fever with a temperature of 100.2°F (37.9°C), which was assumed to be a Jarisch-Herxheimer reaction. The fever resolved by the next morning without further treatment.

His course was otherwise uneventful. The exanthema resolved within 3 months, and his liver function returned to normal. Five months later, the rapid plasma reagin test was repeated on an outpatient basis, and the result was normal.

SYPHILIS IS NOT A DISEASE OF THE PAST

Syphilis is caused by T pallidum and is mainly transmitted by sexual contact.¹

The incidence of syphilis has substantially increased in recent years in Japan^2,3 and worldwide.⁴ The typical patient is a young man who has sex with men, is infected with HIV, and has a history of syphilis infection.³ However, the rapid increase in syphilis infections in Japan in recent years is largely because of an increase in heterosexual transmission.³

Infectious in its early stages

Syphilis is potentially infectious in its early (primary, secondary, and early latent) stages.^1,5 The secondary stage generally begins 6 to 8 weeks after the primary infection¹ and presents with diverse symptoms, including arthralgia, condylomata lata, generalized lymphaden­opathy, maculopapular and papulosquamous exanthema, myalgia, and pharyngitis.¹

Liver dysfunction in secondary syphilis

Liver dysfunction is common in secondary syphilis, occurring in 25% to 50% of cases.⁵ The liver enzyme pattern in most cases is a disproportionate increase in the alkaline phosphatase level compared with modest elevations of aminotransferases and bilirubin.^2,5 However, some cases may show predominant hepatocellular damage (with prominent elevations in aminotransferase levels), and others may present with severe cholestasis (with prominent elevations in alkaline phosphatase and bilirubin) or even fulminant hepatic failure.^2,5

The diagnostic criteria for syphilitic hepatitis are abnormal liver enzyme levels, serologic evidence of syphilis in conjunction with acute clinical presentation of secondary syphilis, exclusion of alternative causes of liver dysfunction, and prompt recovery of liver function after antimicrobial therapy.^2,5

Pathogenic mechanisms in syphilitic hepatitis include direct portal venous inoculation and immune complex-mediated disease.² However, direct hepatotoxicity of the microorganism seems unlikely, as spirochetes are rarely detected in liver specimens.^2,5

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction is an acute febrile illness during the first 24 hours of antimicrobial treatment.^1,6 It is assumed to be due to lysis of large numbers of spirochetes, releasing lipopolysaccharides (endotoxins) that further incite the release of a range of cytokines, resulting in symptoms such as fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.^6,7

The frequency of Jarisch-Herxheimer reaction in syphilis and other spirochetal infections has varied widely in different reports.⁸ It is common in primary and secondary syphilis but usually does not occur in latent syphilis.⁶

Consider the diagnosis

Physicians should consider secondary syphilis in patients who present with characteristic generalized reddish macules and papules with papulosquamous lesions, including on the palms and soles as in our patient, and also in patients who have had unprotected sexual contact. Syphilis is not a disease of the past.

Acknowledgment: The authors thank Dr. Joel Branch, Shonan Kamakura General Hospital, Japan, for his editorial assistance.

WASHINGTON – For male patients with sickle cell disease, priapism can be more than just painful and embarrassing. The prolonged erections prompted by vasoocclusive events in the penis may lead to irreversible impotence, but little is known about risk factors for priapism, which remains a difficult-to-treat complication of the disease.

In males with HbSS sickle cell disease (SCD) and priapism, RBC adhesion is increased in hypoxic conditions, according to preliminary findings from work using a newly developed biochip that mimics microvascular conditions in SCD. This significant level of adhesion prompted by hypoxia was not seen in men who did not have priapism, according to study coauthor Erina Quinn, a research assistant in hematology and oncology at Case Western Reserve University, Cleveland, who presented the results at the annual meeting of the Foundation for Sickle Cell Disease Research.

When hemoglobin desaturation occurs, polymerization can be increased, leading to increased end-organ damage, Ms. Quinn said. The biochip is “an effort to measure cellular adhesion in a clinically meaningful way.” The tool can detect hemoglobin phenotype, differentiating among HbSS, HbSbeta+, and HbSC. It can also measure the degree of hemolysis and RBC deformability.

The biochip “mimics postcapillary flow conditions in microchannels,” Ms. Quinn said. The device forces blood samples through microchannels that are at the diameter of smaller venules, approximately 50 mcm, and at a physiological flow rate ranging from 1-13 mm/sec. The microfluidic channels are coated with laminin, a subendothelial matrix protein implicated in RBC adhesion. A second microfluidic biochip mimics hypoxic conditions.

The study enrolled 26 men with the HbSS genotype, 14 of whom reported priapism, and assessed RBC adhesion in blood samples run though both the SCD-modeled biochip and the hypoxia biochip. Investigators also assessed contemporaneous in vivo hemoglobin desaturation, and looked for associations with the in vitro biochip findings.

Of the 26 participants, 16 also had either nocturnal or exertional hemoglobin desaturation. In addition, 10 participants had both priapism and desaturations. These data were collected by retrospective chart review and patient survey.

Patients with priapism were a mean age of 34 years, compared with a mean age of 29 years for the other participants, a nonsignificant difference. There were no significant differences in mean hemoglobin or bilirubin levels, or in reticulocyte counts, between the two groups.

However, white blood count, absolute neutrophil count, and lactate dehydrogenase levels were significantly higher for men with priapism (P = .022, .037, and .008, respectively). Ferritin levels were higher as well, at a mean 2,433 (plus or minus 2,234) mcg/L for those with priapism, compared with a mean 269 (plus or minus 3,015) mcg/L for those without priapism (P = .031).

When absolute reticulocyte count was mapped against lactate dehydrogenase levels to create a measure of degree of hemolysis, “individuals with priapism had a more hemolytic lab profile,” said Ms. Quinn (P = .0186).

Though 10 of 14 men with priapism had hemoglobin desaturation, compared with 5 of 12 who did not have priapism, the difference was not statistically significant.

When the researchers compared microchip analysis of RBC adhesion, though, they found marked differences in RBC adhesion in hypoxic versus nonhypoxic conditions. Significantly more RBCs were adherent under hypoxic conditions – in the hypoxic biochip – for the patients with priapism than for patients without priapism (mean, 529 vs. 3,268 adherent cells; P = .016).

[email protected]

WASHINGTON – For male patients with sickle cell disease, priapism can be more than just painful and embarrassing. The prolonged erections prompted by vasoocclusive events in the penis may lead to irreversible impotence, but little is known about risk factors for priapism, which remains a difficult-to-treat complication of the disease.

In males with HbSS sickle cell disease (SCD) and priapism, RBC adhesion is increased in hypoxic conditions, according to preliminary findings from work using a newly developed biochip that mimics microvascular conditions in SCD. This significant level of adhesion prompted by hypoxia was not seen in men who did not have priapism, according to study coauthor Erina Quinn, a research assistant in hematology and oncology at Case Western Reserve University, Cleveland, who presented the results at the annual meeting of the Foundation for Sickle Cell Disease Research.

When hemoglobin desaturation occurs, polymerization can be increased, leading to increased end-organ damage, Ms. Quinn said. The biochip is “an effort to measure cellular adhesion in a clinically meaningful way.” The tool can detect hemoglobin phenotype, differentiating among HbSS, HbSbeta+, and HbSC. It can also measure the degree of hemolysis and RBC deformability.

The biochip “mimics postcapillary flow conditions in microchannels,” Ms. Quinn said. The device forces blood samples through microchannels that are at the diameter of smaller venules, approximately 50 mcm, and at a physiological flow rate ranging from 1-13 mm/sec. The microfluidic channels are coated with laminin, a subendothelial matrix protein implicated in RBC adhesion. A second microfluidic biochip mimics hypoxic conditions.

The study enrolled 26 men with the HbSS genotype, 14 of whom reported priapism, and assessed RBC adhesion in blood samples run though both the SCD-modeled biochip and the hypoxia biochip. Investigators also assessed contemporaneous in vivo hemoglobin desaturation, and looked for associations with the in vitro biochip findings.

Of the 26 participants, 16 also had either nocturnal or exertional hemoglobin desaturation. In addition, 10 participants had both priapism and desaturations. These data were collected by retrospective chart review and patient survey.

Patients with priapism were a mean age of 34 years, compared with a mean age of 29 years for the other participants, a nonsignificant difference. There were no significant differences in mean hemoglobin or bilirubin levels, or in reticulocyte counts, between the two groups.

However, white blood count, absolute neutrophil count, and lactate dehydrogenase levels were significantly higher for men with priapism (P = .022, .037, and .008, respectively). Ferritin levels were higher as well, at a mean 2,433 (plus or minus 2,234) mcg/L for those with priapism, compared with a mean 269 (plus or minus 3,015) mcg/L for those without priapism (P = .031).

When absolute reticulocyte count was mapped against lactate dehydrogenase levels to create a measure of degree of hemolysis, “individuals with priapism had a more hemolytic lab profile,” said Ms. Quinn (P = .0186).

Though 10 of 14 men with priapism had hemoglobin desaturation, compared with 5 of 12 who did not have priapism, the difference was not statistically significant.

When the researchers compared microchip analysis of RBC adhesion, though, they found marked differences in RBC adhesion in hypoxic versus nonhypoxic conditions. Significantly more RBCs were adherent under hypoxic conditions – in the hypoxic biochip – for the patients with priapism than for patients without priapism (mean, 529 vs. 3,268 adherent cells; P = .016).

[email protected]

WASHINGTON – For male patients with sickle cell disease, priapism can be more than just painful and embarrassing. The prolonged erections prompted by vasoocclusive events in the penis may lead to irreversible impotence, but little is known about risk factors for priapism, which remains a difficult-to-treat complication of the disease.

In males with HbSS sickle cell disease (SCD) and priapism, RBC adhesion is increased in hypoxic conditions, according to preliminary findings from work using a newly developed biochip that mimics microvascular conditions in SCD. This significant level of adhesion prompted by hypoxia was not seen in men who did not have priapism, according to study coauthor Erina Quinn, a research assistant in hematology and oncology at Case Western Reserve University, Cleveland, who presented the results at the annual meeting of the Foundation for Sickle Cell Disease Research.

When hemoglobin desaturation occurs, polymerization can be increased, leading to increased end-organ damage, Ms. Quinn said. The biochip is “an effort to measure cellular adhesion in a clinically meaningful way.” The tool can detect hemoglobin phenotype, differentiating among HbSS, HbSbeta+, and HbSC. It can also measure the degree of hemolysis and RBC deformability.

The biochip “mimics postcapillary flow conditions in microchannels,” Ms. Quinn said. The device forces blood samples through microchannels that are at the diameter of smaller venules, approximately 50 mcm, and at a physiological flow rate ranging from 1-13 mm/sec. The microfluidic channels are coated with laminin, a subendothelial matrix protein implicated in RBC adhesion. A second microfluidic biochip mimics hypoxic conditions.

The study enrolled 26 men with the HbSS genotype, 14 of whom reported priapism, and assessed RBC adhesion in blood samples run though both the SCD-modeled biochip and the hypoxia biochip. Investigators also assessed contemporaneous in vivo hemoglobin desaturation, and looked for associations with the in vitro biochip findings.

Of the 26 participants, 16 also had either nocturnal or exertional hemoglobin desaturation. In addition, 10 participants had both priapism and desaturations. These data were collected by retrospective chart review and patient survey.

Patients with priapism were a mean age of 34 years, compared with a mean age of 29 years for the other participants, a nonsignificant difference. There were no significant differences in mean hemoglobin or bilirubin levels, or in reticulocyte counts, between the two groups.

However, white blood count, absolute neutrophil count, and lactate dehydrogenase levels were significantly higher for men with priapism (P = .022, .037, and .008, respectively). Ferritin levels were higher as well, at a mean 2,433 (plus or minus 2,234) mcg/L for those with priapism, compared with a mean 269 (plus or minus 3,015) mcg/L for those without priapism (P = .031).

When absolute reticulocyte count was mapped against lactate dehydrogenase levels to create a measure of degree of hemolysis, “individuals with priapism had a more hemolytic lab profile,” said Ms. Quinn (P = .0186).

Though 10 of 14 men with priapism had hemoglobin desaturation, compared with 5 of 12 who did not have priapism, the difference was not statistically significant.

When the researchers compared microchip analysis of RBC adhesion, though, they found marked differences in RBC adhesion in hypoxic versus nonhypoxic conditions. Significantly more RBCs were adherent under hypoxic conditions – in the hypoxic biochip – for the patients with priapism than for patients without priapism (mean, 529 vs. 3,268 adherent cells; P = .016).

[email protected]

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.