In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

PHILADELPHIA – Posttraumatic headache may be associated with quantitative changes in photosensitivity and allodynia, according to results of a pilot study presented at the annual meeting of the American Headache Society. The findings suggest that patients with posttraumatic headache have abnormal, multimodal sensory processing, said Amaal J. Starling, MD, a neurologist at Mayo Clinic in Phoenix.

Mild traumatic brain injury (TBI) is a growing public health problem. Headache is the most common symptom after mild TBI, and often the most debilitating symptom for these patients. No Food and Drug Administration–approved treatments are available for patients with posttraumatic headache, and about three-quarters of these patients report that current treatments bring them no relief.

Identifying novel targets and developing new treatment options will require a deeper understanding of the pathophysiology of posttraumatic headache, said Dr. Starling. She and her colleagues conducted a pilot study to characterize allodynia, cutaneous heat pain thresholds, photophobia, and light-induced pain thresholds objectively in patients with posttraumatic headache, compared with healthy controls.
 

Participants were exposed to a bright-light stressor

The researchers enrolled 20 patients between ages 18 years and 65 years with posttraumatic headache attributed to mild TBI in their study. They matched these patients by age with 20 healthy controls. Dr. Starling and colleagues evaluated all participants prospectively using the Allodynia Symptom Checklist (ASC-12), Photosensitivity Assessment Questionnaire (PAQ), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI).

The investigators performed quantitative sensory testing to measure each participant’s cutaneous forearm heat pain threshold. Using a progressive light stimulation device, they quantified each participant’s light-induced pain threshold. Finally, Dr. Starling and colleagues obtained participants’ cutaneous heat pain thresholds immediately after, 10 minutes after, and 40 minutes after exposing them to a bright-light stressor.

The researchers found no significant differences between groups in age, gender, or race. The population’s average age was 41 years. Approximately 70% of the sample was female. Among participants with posttraumatic headache, the average time since the onset of posttraumatic headache was 46 months. The average number of headache days per month in that group was 17.2, which represented “a significantly high headache burden,” said Dr. Starling. Approximately 80% of patients with posttraumatic headache had headaches with a migraine phenotype.
 

Patients’ pain thresholds were lower

STAI and BDI scores were significantly higher among patients with posttraumatic headache, compared with controls. Mean PAQ score was 0.62 among patients and 0.24 among controls, representing significantly greater photophobia symptom severity among patients, said Dr. Starling.

Light-induced pain thresholds were significantly lower in patients with posttraumatic headache (median, 90.5 lux), compared with healthy controls (median, 863.5 lux), independent of depression and anxiety. Allodynia symptom severity was significantly higher in patients with posttraumatic headache (mean ASC-12 score, 5.7), compared with controls (mean ASC-12 score, 0.98).

In addition, the mean baseline cutaneous heat pain threshold was 40.8° C in patients with posttraumatic headache and 44.4° C in healthy controls. When participants were subjected to the bright-light stressor, the immediate change in heat pain threshold was significant in patients with posttraumatic headache (−1.9° C), compared with healthy controls. The difference between groups was not significant at 10 and 40 minutes after exposure to the stressor, however. The light intensity inducing moderate pain was 688 lux in patients with posttraumatic headache, compared with 6,000 lux in healthy controls.

“Our next steps are going to be replicating this [study] in a larger population, as well as determining whether any type of intervention would change these different types of sensory sensitivities and thresholds,” said Dr. Starling. She and her colleagues will use this human research model to examine whether posttraumatic headache differs from other headache disorders such as migraine and to examine potential differences between acute and persistent posttraumatic headache.

The study was funded through an intramural Mayo Clinic early career research award.

egreb@mdedge.com

SOURCE: Starling AJ et al. AHS 2019. Abstract OR14.

PHILADELPHIA – Posttraumatic headache may be associated with quantitative changes in photosensitivity and allodynia, according to results of a pilot study presented at the annual meeting of the American Headache Society. The findings suggest that patients with posttraumatic headache have abnormal, multimodal sensory processing, said Amaal J. Starling, MD, a neurologist at Mayo Clinic in Phoenix.

Mild traumatic brain injury (TBI) is a growing public health problem. Headache is the most common symptom after mild TBI, and often the most debilitating symptom for these patients. No Food and Drug Administration–approved treatments are available for patients with posttraumatic headache, and about three-quarters of these patients report that current treatments bring them no relief.

Identifying novel targets and developing new treatment options will require a deeper understanding of the pathophysiology of posttraumatic headache, said Dr. Starling. She and her colleagues conducted a pilot study to characterize allodynia, cutaneous heat pain thresholds, photophobia, and light-induced pain thresholds objectively in patients with posttraumatic headache, compared with healthy controls.
 

Participants were exposed to a bright-light stressor

The researchers enrolled 20 patients between ages 18 years and 65 years with posttraumatic headache attributed to mild TBI in their study. They matched these patients by age with 20 healthy controls. Dr. Starling and colleagues evaluated all participants prospectively using the Allodynia Symptom Checklist (ASC-12), Photosensitivity Assessment Questionnaire (PAQ), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI).

The investigators performed quantitative sensory testing to measure each participant’s cutaneous forearm heat pain threshold. Using a progressive light stimulation device, they quantified each participant’s light-induced pain threshold. Finally, Dr. Starling and colleagues obtained participants’ cutaneous heat pain thresholds immediately after, 10 minutes after, and 40 minutes after exposing them to a bright-light stressor.

The researchers found no significant differences between groups in age, gender, or race. The population’s average age was 41 years. Approximately 70% of the sample was female. Among participants with posttraumatic headache, the average time since the onset of posttraumatic headache was 46 months. The average number of headache days per month in that group was 17.2, which represented “a significantly high headache burden,” said Dr. Starling. Approximately 80% of patients with posttraumatic headache had headaches with a migraine phenotype.
 

Patients’ pain thresholds were lower

STAI and BDI scores were significantly higher among patients with posttraumatic headache, compared with controls. Mean PAQ score was 0.62 among patients and 0.24 among controls, representing significantly greater photophobia symptom severity among patients, said Dr. Starling.

Light-induced pain thresholds were significantly lower in patients with posttraumatic headache (median, 90.5 lux), compared with healthy controls (median, 863.5 lux), independent of depression and anxiety. Allodynia symptom severity was significantly higher in patients with posttraumatic headache (mean ASC-12 score, 5.7), compared with controls (mean ASC-12 score, 0.98).

In addition, the mean baseline cutaneous heat pain threshold was 40.8° C in patients with posttraumatic headache and 44.4° C in healthy controls. When participants were subjected to the bright-light stressor, the immediate change in heat pain threshold was significant in patients with posttraumatic headache (−1.9° C), compared with healthy controls. The difference between groups was not significant at 10 and 40 minutes after exposure to the stressor, however. The light intensity inducing moderate pain was 688 lux in patients with posttraumatic headache, compared with 6,000 lux in healthy controls.

“Our next steps are going to be replicating this [study] in a larger population, as well as determining whether any type of intervention would change these different types of sensory sensitivities and thresholds,” said Dr. Starling. She and her colleagues will use this human research model to examine whether posttraumatic headache differs from other headache disorders such as migraine and to examine potential differences between acute and persistent posttraumatic headache.

The study was funded through an intramural Mayo Clinic early career research award.

egreb@mdedge.com

SOURCE: Starling AJ et al. AHS 2019. Abstract OR14.

PHILADELPHIA – Posttraumatic headache may be associated with quantitative changes in photosensitivity and allodynia, according to results of a pilot study presented at the annual meeting of the American Headache Society. The findings suggest that patients with posttraumatic headache have abnormal, multimodal sensory processing, said Amaal J. Starling, MD, a neurologist at Mayo Clinic in Phoenix.

Mild traumatic brain injury (TBI) is a growing public health problem. Headache is the most common symptom after mild TBI, and often the most debilitating symptom for these patients. No Food and Drug Administration–approved treatments are available for patients with posttraumatic headache, and about three-quarters of these patients report that current treatments bring them no relief.

Identifying novel targets and developing new treatment options will require a deeper understanding of the pathophysiology of posttraumatic headache, said Dr. Starling. She and her colleagues conducted a pilot study to characterize allodynia, cutaneous heat pain thresholds, photophobia, and light-induced pain thresholds objectively in patients with posttraumatic headache, compared with healthy controls.
 

Participants were exposed to a bright-light stressor

The researchers enrolled 20 patients between ages 18 years and 65 years with posttraumatic headache attributed to mild TBI in their study. They matched these patients by age with 20 healthy controls. Dr. Starling and colleagues evaluated all participants prospectively using the Allodynia Symptom Checklist (ASC-12), Photosensitivity Assessment Questionnaire (PAQ), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI).

The investigators performed quantitative sensory testing to measure each participant’s cutaneous forearm heat pain threshold. Using a progressive light stimulation device, they quantified each participant’s light-induced pain threshold. Finally, Dr. Starling and colleagues obtained participants’ cutaneous heat pain thresholds immediately after, 10 minutes after, and 40 minutes after exposing them to a bright-light stressor.

The researchers found no significant differences between groups in age, gender, or race. The population’s average age was 41 years. Approximately 70% of the sample was female. Among participants with posttraumatic headache, the average time since the onset of posttraumatic headache was 46 months. The average number of headache days per month in that group was 17.2, which represented “a significantly high headache burden,” said Dr. Starling. Approximately 80% of patients with posttraumatic headache had headaches with a migraine phenotype.
 

Patients’ pain thresholds were lower

STAI and BDI scores were significantly higher among patients with posttraumatic headache, compared with controls. Mean PAQ score was 0.62 among patients and 0.24 among controls, representing significantly greater photophobia symptom severity among patients, said Dr. Starling.

Light-induced pain thresholds were significantly lower in patients with posttraumatic headache (median, 90.5 lux), compared with healthy controls (median, 863.5 lux), independent of depression and anxiety. Allodynia symptom severity was significantly higher in patients with posttraumatic headache (mean ASC-12 score, 5.7), compared with controls (mean ASC-12 score, 0.98).

In addition, the mean baseline cutaneous heat pain threshold was 40.8° C in patients with posttraumatic headache and 44.4° C in healthy controls. When participants were subjected to the bright-light stressor, the immediate change in heat pain threshold was significant in patients with posttraumatic headache (−1.9° C), compared with healthy controls. The difference between groups was not significant at 10 and 40 minutes after exposure to the stressor, however. The light intensity inducing moderate pain was 688 lux in patients with posttraumatic headache, compared with 6,000 lux in healthy controls.

“Our next steps are going to be replicating this [study] in a larger population, as well as determining whether any type of intervention would change these different types of sensory sensitivities and thresholds,” said Dr. Starling. She and her colleagues will use this human research model to examine whether posttraumatic headache differs from other headache disorders such as migraine and to examine potential differences between acute and persistent posttraumatic headache.

The study was funded through an intramural Mayo Clinic early career research award.

egreb@mdedge.com

SOURCE: Starling AJ et al. AHS 2019. Abstract OR14.

Click here to read the supplement.

The 2019 Pediatric Dermatology supplement features a selection of articles published in Dermatology News and Pediatric News, with commentary by Lawrence F. Eichenfield, MD, and Robert Sidbury, MD.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. He is vice chair of dermatology and professor of dermatology and pediatrics at the University of California, San Diego.

Dr. Sidbury is chief of dermatology at Seattle Children’s Hospital and professor, department of pediatrics, University of Washington, Seattle.

Highlights include:

• Atopic dermatitis update: The field continues to evolve
• When treating impetigo, be aware of antibiotic resistance patterns
• Don’t sweat axillary hyperhidrosis
• Premature children’s skin is different

Click here to read the supplement.

Click here to read the supplement.

The 2019 Pediatric Dermatology supplement features a selection of articles published in Dermatology News and Pediatric News, with commentary by Lawrence F. Eichenfield, MD, and Robert Sidbury, MD.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. He is vice chair of dermatology and professor of dermatology and pediatrics at the University of California, San Diego.

Dr. Sidbury is chief of dermatology at Seattle Children’s Hospital and professor, department of pediatrics, University of Washington, Seattle.

Highlights include:

• Atopic dermatitis update: The field continues to evolve
• When treating impetigo, be aware of antibiotic resistance patterns
• Don’t sweat axillary hyperhidrosis
• Premature children’s skin is different

Click here to read the supplement.

Click here to read the supplement.

The 2019 Pediatric Dermatology supplement features a selection of articles published in Dermatology News and Pediatric News, with commentary by Lawrence F. Eichenfield, MD, and Robert Sidbury, MD.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. He is vice chair of dermatology and professor of dermatology and pediatrics at the University of California, San Diego.

Dr. Sidbury is chief of dermatology at Seattle Children’s Hospital and professor, department of pediatrics, University of Washington, Seattle.

Highlights include:

• Atopic dermatitis update: The field continues to evolve
• When treating impetigo, be aware of antibiotic resistance patterns
• Don’t sweat axillary hyperhidrosis
• Premature children’s skin is different

Click here to read the supplement.

AUSTIN, TEX. – The way Adelaide A. Hebert, MD, sees it, the decision to add clinical research to your existing dermatology practice requires some soul searching, because not everyone is cut out for it.

“This is not something you take lightly,” Dr. Hebert, chief of pediatric dermatology at the University of Texas Health Science Center, Houston, said at the annual meeting of the Society for Pediatric Dermatology. “There will be days when you feel like you are going into combat. If you are not prepared for that, maybe stick to clinical practice. That plan might be a bit simpler.”

For more than 30 years, Dr. Hebert has been engaged in dermatology clinical research, with a focus on atopic dermatitis, psoriasis, and hyperhidrosis. Her team includes a full-time research fellow, a full-time nurse practitioner, and a part-time clinical trials coordinator. “We work very hard, and I am responsible for their salaries,” she said. “There is considerable pressure from year to year, but they work hard and are very loyal. They represent a great portion of the success that we have in clinical research. You need a team, and you have to be a team leader in order to undertake this.”

Dr. Hebert offered the following tips for incorporating clinical research into your practice:

• Set aside allocated time. “This is not a side job within your current occupation,” she emphasized. “You really need allocated time to do research, and you need protected academic time if you work in that environment. You also need protected academic time for your staff to conduct research.”

• Get to know the players involved. This includes forming professional relationships with internal and external review boards, and understanding contract and grants. “This collaboration is a lot like getting into a sport,” she explained. “You have to know the rules, you have to know how to play with strategy, and you have to be very effective.”

Review boards that work with academic centers include the Western Institutional Review Board (WIRB) and Advarra. “You also need to understand time lines, what it takes to go from submission to implementation,” Dr. Hebert said. “That time cannot be too long, or you will be off the list of desired investigators because you cannot get up and running in a timely fashion. Your team has to be behind you in order to make this happen.” [She recommended the National Association of Healthcare Revenue Integrity publication, “The Practical Guide to Clinical Trials Billing.”]

• Consider space and equipment needs. This includes space for patient charts, cameras, scales, electronic devices for data capture, computer equipment, and other instruments you may need to carry out your work. Dr. Hebert’s clinic houses about a half-dozen EKG machines dedicated to research projects. “You also need a lot of storage,” she added. “Our university requires us to save every piece of paper, every communication for 15 years. Our university does allocate that space.”

Sponsored research opportunities include working with the National Institutes of Health, Department of Defense, pharmaceutical companies, and over-the-counter product companies. “You can also initiate your own research,” she said. “One way to get started is to partner with an established researcher. That could be someone in your department, in a different department, or in a clinical research unit within your institution. They can help you with infrastructure and they can sometimes do your research submissions for you.”

Other ways to explore research opportunities include reaching out to medical science liaisons and clinical trial research organizations, and hiring fellows with research experience. “The bottom line is, talk to a lot of people you do not know,” Dr. Hebert said. “That is the real secret to getting research studies.”

There is another player in the field to become familiar with: contract research organizations (CROs), which provide support to pharmaceutical industries in the form of research services outsourced on a contract basis. They receive payment from the sponsor to conduct clinical research operations. “Many times the sponsor does not entirely know what the CRO is doing with regard to the interface with you as an investigator,” said Dr. Hebert, who has conducted more than 160 trials, including 65 in atopic dermatitis alone. “Sometimes you have to go over the head of the CRO to address issues that come up. The reality is, if the sponsor does not know you are not getting paid or having obstacles put in front of you that may not be in your contract, that constitutes a problem. You have to learn to be a bit shrewd in this game of research.”

She added that clinicians who choose to conduct clinical research come to learn “a whole new language,” such as what a confidential disclosure agreement is. “You also have to undergo CITI [Collaborative Institutional Training Initiative] training to meet the principles of good clinical practice,” she said. Other specifics include infectious substance shipping training per International Air Transport Association shipping guidelines, protocol training in arenas such as Eczema Area and Severity Index scoring and Psoriasis Area Severity Index scoring, and electronic case report form/electronic data–capture report training. “We also have a lot of equipment training because we are constantly getting new tablets for recording patient data and so forth,” she said. “This is something that has helped me become more technically equipped to handle all of this data capture.”

Dr. Hebert closed her remarks by noting that conducting clinical research can be a rewarding endeavor. “You really do address unmet needs, and you give a lot of education to residents, students, and fellows,” she said. “Clinical research provides research opportunities for those interested in dermatology. You have those moments when you see patients get better, and this represents the best patient encounter you could ever hope for.”

She reported having no relevant financial disclosures.

dbrunk@mdedge.com

AUSTIN, TEX. – The way Adelaide A. Hebert, MD, sees it, the decision to add clinical research to your existing dermatology practice requires some soul searching, because not everyone is cut out for it.

“This is not something you take lightly,” Dr. Hebert, chief of pediatric dermatology at the University of Texas Health Science Center, Houston, said at the annual meeting of the Society for Pediatric Dermatology. “There will be days when you feel like you are going into combat. If you are not prepared for that, maybe stick to clinical practice. That plan might be a bit simpler.”

For more than 30 years, Dr. Hebert has been engaged in dermatology clinical research, with a focus on atopic dermatitis, psoriasis, and hyperhidrosis. Her team includes a full-time research fellow, a full-time nurse practitioner, and a part-time clinical trials coordinator. “We work very hard, and I am responsible for their salaries,” she said. “There is considerable pressure from year to year, but they work hard and are very loyal. They represent a great portion of the success that we have in clinical research. You need a team, and you have to be a team leader in order to undertake this.”

Dr. Hebert offered the following tips for incorporating clinical research into your practice:

• Set aside allocated time. “This is not a side job within your current occupation,” she emphasized. “You really need allocated time to do research, and you need protected academic time if you work in that environment. You also need protected academic time for your staff to conduct research.”

• Get to know the players involved. This includes forming professional relationships with internal and external review boards, and understanding contract and grants. “This collaboration is a lot like getting into a sport,” she explained. “You have to know the rules, you have to know how to play with strategy, and you have to be very effective.”

Review boards that work with academic centers include the Western Institutional Review Board (WIRB) and Advarra. “You also need to understand time lines, what it takes to go from submission to implementation,” Dr. Hebert said. “That time cannot be too long, or you will be off the list of desired investigators because you cannot get up and running in a timely fashion. Your team has to be behind you in order to make this happen.” [She recommended the National Association of Healthcare Revenue Integrity publication, “The Practical Guide to Clinical Trials Billing.”]

• Consider space and equipment needs. This includes space for patient charts, cameras, scales, electronic devices for data capture, computer equipment, and other instruments you may need to carry out your work. Dr. Hebert’s clinic houses about a half-dozen EKG machines dedicated to research projects. “You also need a lot of storage,” she added. “Our university requires us to save every piece of paper, every communication for 15 years. Our university does allocate that space.”

Sponsored research opportunities include working with the National Institutes of Health, Department of Defense, pharmaceutical companies, and over-the-counter product companies. “You can also initiate your own research,” she said. “One way to get started is to partner with an established researcher. That could be someone in your department, in a different department, or in a clinical research unit within your institution. They can help you with infrastructure and they can sometimes do your research submissions for you.”

Other ways to explore research opportunities include reaching out to medical science liaisons and clinical trial research organizations, and hiring fellows with research experience. “The bottom line is, talk to a lot of people you do not know,” Dr. Hebert said. “That is the real secret to getting research studies.”

There is another player in the field to become familiar with: contract research organizations (CROs), which provide support to pharmaceutical industries in the form of research services outsourced on a contract basis. They receive payment from the sponsor to conduct clinical research operations. “Many times the sponsor does not entirely know what the CRO is doing with regard to the interface with you as an investigator,” said Dr. Hebert, who has conducted more than 160 trials, including 65 in atopic dermatitis alone. “Sometimes you have to go over the head of the CRO to address issues that come up. The reality is, if the sponsor does not know you are not getting paid or having obstacles put in front of you that may not be in your contract, that constitutes a problem. You have to learn to be a bit shrewd in this game of research.”

She added that clinicians who choose to conduct clinical research come to learn “a whole new language,” such as what a confidential disclosure agreement is. “You also have to undergo CITI [Collaborative Institutional Training Initiative] training to meet the principles of good clinical practice,” she said. Other specifics include infectious substance shipping training per International Air Transport Association shipping guidelines, protocol training in arenas such as Eczema Area and Severity Index scoring and Psoriasis Area Severity Index scoring, and electronic case report form/electronic data–capture report training. “We also have a lot of equipment training because we are constantly getting new tablets for recording patient data and so forth,” she said. “This is something that has helped me become more technically equipped to handle all of this data capture.”

Dr. Hebert closed her remarks by noting that conducting clinical research can be a rewarding endeavor. “You really do address unmet needs, and you give a lot of education to residents, students, and fellows,” she said. “Clinical research provides research opportunities for those interested in dermatology. You have those moments when you see patients get better, and this represents the best patient encounter you could ever hope for.”

She reported having no relevant financial disclosures.

dbrunk@mdedge.com

AUSTIN, TEX. – The way Adelaide A. Hebert, MD, sees it, the decision to add clinical research to your existing dermatology practice requires some soul searching, because not everyone is cut out for it.

“This is not something you take lightly,” Dr. Hebert, chief of pediatric dermatology at the University of Texas Health Science Center, Houston, said at the annual meeting of the Society for Pediatric Dermatology. “There will be days when you feel like you are going into combat. If you are not prepared for that, maybe stick to clinical practice. That plan might be a bit simpler.”

For more than 30 years, Dr. Hebert has been engaged in dermatology clinical research, with a focus on atopic dermatitis, psoriasis, and hyperhidrosis. Her team includes a full-time research fellow, a full-time nurse practitioner, and a part-time clinical trials coordinator. “We work very hard, and I am responsible for their salaries,” she said. “There is considerable pressure from year to year, but they work hard and are very loyal. They represent a great portion of the success that we have in clinical research. You need a team, and you have to be a team leader in order to undertake this.”

Dr. Hebert offered the following tips for incorporating clinical research into your practice:

• Set aside allocated time. “This is not a side job within your current occupation,” she emphasized. “You really need allocated time to do research, and you need protected academic time if you work in that environment. You also need protected academic time for your staff to conduct research.”

• Get to know the players involved. This includes forming professional relationships with internal and external review boards, and understanding contract and grants. “This collaboration is a lot like getting into a sport,” she explained. “You have to know the rules, you have to know how to play with strategy, and you have to be very effective.”

Review boards that work with academic centers include the Western Institutional Review Board (WIRB) and Advarra. “You also need to understand time lines, what it takes to go from submission to implementation,” Dr. Hebert said. “That time cannot be too long, or you will be off the list of desired investigators because you cannot get up and running in a timely fashion. Your team has to be behind you in order to make this happen.” [She recommended the National Association of Healthcare Revenue Integrity publication, “The Practical Guide to Clinical Trials Billing.”]

• Consider space and equipment needs. This includes space for patient charts, cameras, scales, electronic devices for data capture, computer equipment, and other instruments you may need to carry out your work. Dr. Hebert’s clinic houses about a half-dozen EKG machines dedicated to research projects. “You also need a lot of storage,” she added. “Our university requires us to save every piece of paper, every communication for 15 years. Our university does allocate that space.”

Sponsored research opportunities include working with the National Institutes of Health, Department of Defense, pharmaceutical companies, and over-the-counter product companies. “You can also initiate your own research,” she said. “One way to get started is to partner with an established researcher. That could be someone in your department, in a different department, or in a clinical research unit within your institution. They can help you with infrastructure and they can sometimes do your research submissions for you.”

Other ways to explore research opportunities include reaching out to medical science liaisons and clinical trial research organizations, and hiring fellows with research experience. “The bottom line is, talk to a lot of people you do not know,” Dr. Hebert said. “That is the real secret to getting research studies.”

There is another player in the field to become familiar with: contract research organizations (CROs), which provide support to pharmaceutical industries in the form of research services outsourced on a contract basis. They receive payment from the sponsor to conduct clinical research operations. “Many times the sponsor does not entirely know what the CRO is doing with regard to the interface with you as an investigator,” said Dr. Hebert, who has conducted more than 160 trials, including 65 in atopic dermatitis alone. “Sometimes you have to go over the head of the CRO to address issues that come up. The reality is, if the sponsor does not know you are not getting paid or having obstacles put in front of you that may not be in your contract, that constitutes a problem. You have to learn to be a bit shrewd in this game of research.”

She added that clinicians who choose to conduct clinical research come to learn “a whole new language,” such as what a confidential disclosure agreement is. “You also have to undergo CITI [Collaborative Institutional Training Initiative] training to meet the principles of good clinical practice,” she said. Other specifics include infectious substance shipping training per International Air Transport Association shipping guidelines, protocol training in arenas such as Eczema Area and Severity Index scoring and Psoriasis Area Severity Index scoring, and electronic case report form/electronic data–capture report training. “We also have a lot of equipment training because we are constantly getting new tablets for recording patient data and so forth,” she said. “This is something that has helped me become more technically equipped to handle all of this data capture.”

Dr. Hebert closed her remarks by noting that conducting clinical research can be a rewarding endeavor. “You really do address unmet needs, and you give a lot of education to residents, students, and fellows,” she said. “Clinical research provides research opportunities for those interested in dermatology. You have those moments when you see patients get better, and this represents the best patient encounter you could ever hope for.”

She reported having no relevant financial disclosures.

dbrunk@mdedge.com

The Food and Drug Administration has approved pembrolizumab (Keytruda) for patients with recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on results of two clinical trials: KEYNOTE-180 and KEYNOTE-181. KEYNOTE-181 was a randomized, open-label, active-controlled trial of 628 patients with recurrent, locally advanced, or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced or metastatic disease. Patients who received pembrolizumab had a median overall survival of 10.3 months, compared with 6.7 months for patients who received control drugs.

In KEYNOTE-180, a single-arm, open-label trial of 121 patients with esophageal cancer who progressed after two prior lines of treatment, patients who had a PD-L1 combined positive score of at least 10 had an overall response rate of 20%, with response durations ranging from 4.2 to over 25.1 months, and with 71% of those patients having a response time over 6 months.

Adverse reactions reported in KEYNOTE-180 and –181 were similar to those in previous trials involving pembrolizumab in patients with melanoma and non–small cell lung cancer. The most common reactions were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

The PD-L1 IHC 22C3 pharmDx kit was approved as the companion diagnostic device, the FDA said.

Find the full press release on the FDA website.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for patients with recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on results of two clinical trials: KEYNOTE-180 and KEYNOTE-181. KEYNOTE-181 was a randomized, open-label, active-controlled trial of 628 patients with recurrent, locally advanced, or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced or metastatic disease. Patients who received pembrolizumab had a median overall survival of 10.3 months, compared with 6.7 months for patients who received control drugs.

In KEYNOTE-180, a single-arm, open-label trial of 121 patients with esophageal cancer who progressed after two prior lines of treatment, patients who had a PD-L1 combined positive score of at least 10 had an overall response rate of 20%, with response durations ranging from 4.2 to over 25.1 months, and with 71% of those patients having a response time over 6 months.

Adverse reactions reported in KEYNOTE-180 and –181 were similar to those in previous trials involving pembrolizumab in patients with melanoma and non–small cell lung cancer. The most common reactions were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

The PD-L1 IHC 22C3 pharmDx kit was approved as the companion diagnostic device, the FDA said.

Find the full press release on the FDA website.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for patients with recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on results of two clinical trials: KEYNOTE-180 and KEYNOTE-181. KEYNOTE-181 was a randomized, open-label, active-controlled trial of 628 patients with recurrent, locally advanced, or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced or metastatic disease. Patients who received pembrolizumab had a median overall survival of 10.3 months, compared with 6.7 months for patients who received control drugs.

In KEYNOTE-180, a single-arm, open-label trial of 121 patients with esophageal cancer who progressed after two prior lines of treatment, patients who had a PD-L1 combined positive score of at least 10 had an overall response rate of 20%, with response durations ranging from 4.2 to over 25.1 months, and with 71% of those patients having a response time over 6 months.

Adverse reactions reported in KEYNOTE-180 and –181 were similar to those in previous trials involving pembrolizumab in patients with melanoma and non–small cell lung cancer. The most common reactions were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

The PD-L1 IHC 22C3 pharmDx kit was approved as the companion diagnostic device, the FDA said.

Find the full press release on the FDA website.

Following therapy with curative intent for early-stage primary breast care, the presence of circulating tumor DNA may identify those patients at high risk for relapse, investigators reported.

Among 101 women treated for early-stage breast cancer and followed for a median of nearly 3 years, detection of circulating tumor DNA (ctDNA) during follow-up was associated with a 2,400% increased risk for relapse, and detection of ctDNA at diagnosis but before treatment was associated with a nearly 500% risk, wrote Isaac Garcia-Murillas, PhD, of the Institute of Cancer Research, London, and colleagues.

“Prospective clinical trials are now required to assess whether detection of ctDNA can improve outcomes in patients, and a phase 2 interventional trial in TNBC [triple-negative breast cancer] has been initiated. This trial may develop a new treatment paradigm for treating breast cancer, in which treatment is initiated at molecular relapse without waiting for symptomatic incurable metastatic disease to develop,” they wrote in JAMA Oncology.

The investigators conducted a prospective, multicenter validation study of samples collected from women with early-stage breast cancer irrespective of hormone-receptor or HER2 status. The patients were scheduled for neoadjuvant chemotherapy followed by surgery, or surgery followed by adjuvant therapy.

Of 170 women recruited, 101 had tumors with identified mutations and were included in the main cohort. The investigators also conducted secondary analyses with patients in this cohort plus an additional 43 women who had participated in a previous proof-of-principle study.

They first sequenced tumor DNA to identify somatic mutations in primary tumors that could then be tracked using a breast cancer driver gene panel. For each sample, a personalized digital polymerase chain reaction (dPCR) assay was created to identify the mutations in plasma samples.

The plasma samples were collected every 3 months for the first year of follow-up, then every 6 months thereafter.

In the main cohort, the median age was 54 years, and the median follow-up was 35.5 months. The investigators found that, for the primary endpoint of relapse-free survival, ctDNA was associated with a hazard ratio for relapse of 25.2 (P less than .001). Detection of ctDNA in samples taken at the time of diagnosis was also associated with worse relapse-free survival, with an HR of 5.8 (P = .01).

In a secondary analysis, ctDNA detection preceded clinical relapse by a median of 10.7 months, and was associated with relapse in all breast cancer subtypes.

Of 29 patients who experienced a relapse, 22 of 23 with extracranial distant metastatic relapse had prior ctDNA detection.

The remaining six patients experienced relapse without ctDNA detection either before or at the time of relapse. Each of these six patients had a relapse at a single site: in the brain in three patients (with no extracranial relapses), in the ovaries in one patient, and solitary locoregional relapses in two patients.

The investigators acknowledged that the results “demonstrate clinical validity for ctDNA mutation tracking with dPCR but do not demonstrate clinical utility. Without evidence that mutation tracking can improve patient outcome, our results should not be recommended yet for routine clinical practice.”

The study was funded by Breast Cancer Now, Le Cure, and National Institute for Health Research funding to the Biomedical Research Centre at the Royal Marsden Hospital and the Institute of Cancer Research. Dr. Garcia-Murillas had no disclosures. Multiple coauthors reported grants and/or fees from various pharmaceutical companies.

SOURCE: Garcia-Murillias I et al. JAMA Oncol. 2019 Aug 1. doi: 10.1001/jamaoncol.2019.1838.

Following therapy with curative intent for early-stage primary breast care, the presence of circulating tumor DNA may identify those patients at high risk for relapse, investigators reported.

Among 101 women treated for early-stage breast cancer and followed for a median of nearly 3 years, detection of circulating tumor DNA (ctDNA) during follow-up was associated with a 2,400% increased risk for relapse, and detection of ctDNA at diagnosis but before treatment was associated with a nearly 500% risk, wrote Isaac Garcia-Murillas, PhD, of the Institute of Cancer Research, London, and colleagues.

“Prospective clinical trials are now required to assess whether detection of ctDNA can improve outcomes in patients, and a phase 2 interventional trial in TNBC [triple-negative breast cancer] has been initiated. This trial may develop a new treatment paradigm for treating breast cancer, in which treatment is initiated at molecular relapse without waiting for symptomatic incurable metastatic disease to develop,” they wrote in JAMA Oncology.

The investigators conducted a prospective, multicenter validation study of samples collected from women with early-stage breast cancer irrespective of hormone-receptor or HER2 status. The patients were scheduled for neoadjuvant chemotherapy followed by surgery, or surgery followed by adjuvant therapy.

Of 170 women recruited, 101 had tumors with identified mutations and were included in the main cohort. The investigators also conducted secondary analyses with patients in this cohort plus an additional 43 women who had participated in a previous proof-of-principle study.

They first sequenced tumor DNA to identify somatic mutations in primary tumors that could then be tracked using a breast cancer driver gene panel. For each sample, a personalized digital polymerase chain reaction (dPCR) assay was created to identify the mutations in plasma samples.

The plasma samples were collected every 3 months for the first year of follow-up, then every 6 months thereafter.

In the main cohort, the median age was 54 years, and the median follow-up was 35.5 months. The investigators found that, for the primary endpoint of relapse-free survival, ctDNA was associated with a hazard ratio for relapse of 25.2 (P less than .001). Detection of ctDNA in samples taken at the time of diagnosis was also associated with worse relapse-free survival, with an HR of 5.8 (P = .01).

In a secondary analysis, ctDNA detection preceded clinical relapse by a median of 10.7 months, and was associated with relapse in all breast cancer subtypes.

Of 29 patients who experienced a relapse, 22 of 23 with extracranial distant metastatic relapse had prior ctDNA detection.

The remaining six patients experienced relapse without ctDNA detection either before or at the time of relapse. Each of these six patients had a relapse at a single site: in the brain in three patients (with no extracranial relapses), in the ovaries in one patient, and solitary locoregional relapses in two patients.

The investigators acknowledged that the results “demonstrate clinical validity for ctDNA mutation tracking with dPCR but do not demonstrate clinical utility. Without evidence that mutation tracking can improve patient outcome, our results should not be recommended yet for routine clinical practice.”

The study was funded by Breast Cancer Now, Le Cure, and National Institute for Health Research funding to the Biomedical Research Centre at the Royal Marsden Hospital and the Institute of Cancer Research. Dr. Garcia-Murillas had no disclosures. Multiple coauthors reported grants and/or fees from various pharmaceutical companies.

SOURCE: Garcia-Murillias I et al. JAMA Oncol. 2019 Aug 1. doi: 10.1001/jamaoncol.2019.1838.

Following therapy with curative intent for early-stage primary breast care, the presence of circulating tumor DNA may identify those patients at high risk for relapse, investigators reported.

Among 101 women treated for early-stage breast cancer and followed for a median of nearly 3 years, detection of circulating tumor DNA (ctDNA) during follow-up was associated with a 2,400% increased risk for relapse, and detection of ctDNA at diagnosis but before treatment was associated with a nearly 500% risk, wrote Isaac Garcia-Murillas, PhD, of the Institute of Cancer Research, London, and colleagues.

“Prospective clinical trials are now required to assess whether detection of ctDNA can improve outcomes in patients, and a phase 2 interventional trial in TNBC [triple-negative breast cancer] has been initiated. This trial may develop a new treatment paradigm for treating breast cancer, in which treatment is initiated at molecular relapse without waiting for symptomatic incurable metastatic disease to develop,” they wrote in JAMA Oncology.

The investigators conducted a prospective, multicenter validation study of samples collected from women with early-stage breast cancer irrespective of hormone-receptor or HER2 status. The patients were scheduled for neoadjuvant chemotherapy followed by surgery, or surgery followed by adjuvant therapy.

Of 170 women recruited, 101 had tumors with identified mutations and were included in the main cohort. The investigators also conducted secondary analyses with patients in this cohort plus an additional 43 women who had participated in a previous proof-of-principle study.

They first sequenced tumor DNA to identify somatic mutations in primary tumors that could then be tracked using a breast cancer driver gene panel. For each sample, a personalized digital polymerase chain reaction (dPCR) assay was created to identify the mutations in plasma samples.

The plasma samples were collected every 3 months for the first year of follow-up, then every 6 months thereafter.

In the main cohort, the median age was 54 years, and the median follow-up was 35.5 months. The investigators found that, for the primary endpoint of relapse-free survival, ctDNA was associated with a hazard ratio for relapse of 25.2 (P less than .001). Detection of ctDNA in samples taken at the time of diagnosis was also associated with worse relapse-free survival, with an HR of 5.8 (P = .01).

In a secondary analysis, ctDNA detection preceded clinical relapse by a median of 10.7 months, and was associated with relapse in all breast cancer subtypes.

Of 29 patients who experienced a relapse, 22 of 23 with extracranial distant metastatic relapse had prior ctDNA detection.

The remaining six patients experienced relapse without ctDNA detection either before or at the time of relapse. Each of these six patients had a relapse at a single site: in the brain in three patients (with no extracranial relapses), in the ovaries in one patient, and solitary locoregional relapses in two patients.

The investigators acknowledged that the results “demonstrate clinical validity for ctDNA mutation tracking with dPCR but do not demonstrate clinical utility. Without evidence that mutation tracking can improve patient outcome, our results should not be recommended yet for routine clinical practice.”

The study was funded by Breast Cancer Now, Le Cure, and National Institute for Health Research funding to the Biomedical Research Centre at the Royal Marsden Hospital and the Institute of Cancer Research. Dr. Garcia-Murillas had no disclosures. Multiple coauthors reported grants and/or fees from various pharmaceutical companies.

SOURCE: Garcia-Murillias I et al. JAMA Oncol. 2019 Aug 1. doi: 10.1001/jamaoncol.2019.1838.

Key clinical point: Managing comorbid psychiatric disorders in patients with MS could reduce the burden of functional GI disorders.

Major finding: Approximately 42% of patients with MS report functional GI disorders.

Study details: A survey of 6,312 participants in the North American Research Committee on MS Registry.

Disclosures: The study had no sponsor. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.

Citation: Marrie RA et al. CMSC 2019, Abstract QOL13.

Key clinical point: Managing comorbid psychiatric disorders in patients with MS could reduce the burden of functional GI disorders.

Major finding: Approximately 42% of patients with MS report functional GI disorders.

Study details: A survey of 6,312 participants in the North American Research Committee on MS Registry.

Disclosures: The study had no sponsor. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.

Citation: Marrie RA et al. CMSC 2019, Abstract QOL13.

Key clinical point: Managing comorbid psychiatric disorders in patients with MS could reduce the burden of functional GI disorders.

Major finding: Approximately 42% of patients with MS report functional GI disorders.

Study details: A survey of 6,312 participants in the North American Research Committee on MS Registry.

Disclosures: The study had no sponsor. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.

Citation: Marrie RA et al. CMSC 2019, Abstract QOL13.

Key clinical point: Patients with relapsing-remitting MS gain comparable benefits from cladribine therapy, regardless of age.

Major finding: The annual rate of qualifying relapses was 0.14 for treated patients older than 45 years and 0.15 for treated patients aged 45 or younger.

Study details: A post hoc analysis of data from the CLARITY and CLARITY extension studies, which included 870 patients.

Disclosures: Merck KGaA, which manufactures and markets cladribine, supported the study. Several of the investigators have received speaker honoraria, consulting fees, or other funding from Merck KGaA.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with relapsing-remitting MS gain comparable benefits from cladribine therapy, regardless of age.

Major finding: The annual rate of qualifying relapses was 0.14 for treated patients older than 45 years and 0.15 for treated patients aged 45 or younger.

Study details: A post hoc analysis of data from the CLARITY and CLARITY extension studies, which included 870 patients.

Disclosures: Merck KGaA, which manufactures and markets cladribine, supported the study. Several of the investigators have received speaker honoraria, consulting fees, or other funding from Merck KGaA.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with relapsing-remitting MS gain comparable benefits from cladribine therapy, regardless of age.

Major finding: The annual rate of qualifying relapses was 0.14 for treated patients older than 45 years and 0.15 for treated patients aged 45 or younger.

Study details: A post hoc analysis of data from the CLARITY and CLARITY extension studies, which included 870 patients.

Disclosures: Merck KGaA, which manufactures and markets cladribine, supported the study. Several of the investigators have received speaker honoraria, consulting fees, or other funding from Merck KGaA.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Treatment with evobrutinib reduced the number of enhancing lesions versus placebo in patients with relapsing multiple sclerosis, supporting further development of this Bruton’s tyrosine kinase (BTK) inhibitor.

Major finding: The cumulative number of MRI-assessed T1 Gd+ lesions from weeks 12-24 was significantly reduced versus placebo; lesion rate ratios were 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively.

Study details: Forty-eight-week results of a randomized, phase 2, placebo-controlled study of 267 patients with relapsing multiple sclerosis.

Disclosures: Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.

Citation: Montalban X et al. AAN 2019. Abstract S56.004.

Key clinical point: Treatment with evobrutinib reduced the number of enhancing lesions versus placebo in patients with relapsing multiple sclerosis, supporting further development of this Bruton’s tyrosine kinase (BTK) inhibitor.

Major finding: The cumulative number of MRI-assessed T1 Gd+ lesions from weeks 12-24 was significantly reduced versus placebo; lesion rate ratios were 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively.

Study details: Forty-eight-week results of a randomized, phase 2, placebo-controlled study of 267 patients with relapsing multiple sclerosis.

Disclosures: Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.

Citation: Montalban X et al. AAN 2019. Abstract S56.004.

Key clinical point: Treatment with evobrutinib reduced the number of enhancing lesions versus placebo in patients with relapsing multiple sclerosis, supporting further development of this Bruton’s tyrosine kinase (BTK) inhibitor.

Major finding: The cumulative number of MRI-assessed T1 Gd+ lesions from weeks 12-24 was significantly reduced versus placebo; lesion rate ratios were 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively.

Study details: Forty-eight-week results of a randomized, phase 2, placebo-controlled study of 267 patients with relapsing multiple sclerosis.

Disclosures: Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.

Citation: Montalban X et al. AAN 2019. Abstract S56.004.

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.