The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Stop us if you’ve heard this one

Dean Bertoncelj/iStockphoto

An elephant, a capybara, and a horse walk into a bar …

What? You’ve heard it? Really? … No, not really? You were just pulling our leg. Very funny.

Can we go on now? You’re sure? Because if there’s one thing we love, it’s reader participation.

Anyway, there’s this bar, and a bunch of researchers from the University of California’s San Diego and Berkeley campuses are hanging out with a bear, a boar, a javelina (looks and sounds like a pig, about the size of a border collie), and a giraffe when the aforementioned trio shows up.

They see all these mammals together and get an idea. Why not compare the tensile strength of their hair with that of a human adult and child? The next day, after sobering up, they started collecting hair samples.[Legal note: The situation at the bar is a literary device. At no time did the investigators conduct any of their work in such a place.]

Once that was done, uniaxial tension tests were conducted, as you would expect, using an Instron 3342 universal testing system equipped with a 500-N load cell at a strain rate of 10^–2s^–1.

The results, however, were not expected. Thin hairs are stronger than thick hairs. Hair from a human, with an average diameter of about 60 mcm, is stronger than hair from a boar (average diameter, 235 mcm) or a horse (average diameter, 200 mcm), and the weakest hair of all came from an elephant (diameter of 345 mcm) and a giraffe (diameter of 370 mcm). Also, the hair from the 9-year-old child is stronger than the thicker hair of the 30-year-old adult.

The results show that the inherent strength of human hair’s hierarchical structure – an outer layer, or cuticle, “wraps around an inner cortex made of many small fibers linked by chemical bonds” – makes it resistant to deformation, the investigators explained. They hope that synthetic materials with a similar structure could become lighter and stronger in the future.

Now what? The punchline? All this valuable hair information isn’t enough? Fine.

The shocked bartender, who’s already got the makings of a small zoo in his establishment, points a finger in alarm at the latest arrivals and yells, “Hey!” The horse says, “You read my mind, buddy.”


 

Boiled type 2 diabetes

amenic181/Getty Images

Ah, coffee. Is there anything it can’t do? From speeding up delivery of this tardy column (if not boosting its comedy quotient) to reducing the risk of type 2 diabetes, the magic bean seems nearly omnipotent. But java’s magical metabolic properties may be entirely dependent on how you brew your brown elixir.

Coffee-fueled Scandinavians have determined that the stimulating liquid’s antidiabetes effect is only possible when you don’t boil your beans. For those eager to ward off type 2 diabetes, filtered coffee – not boiled coffee – is the ticket to lower insulin resistance.

Researchers at Chalmers University of Technology in Gothenburg, Sweden, and Umeå (Sweden) University identified biomarkers that distinguished the consumption of filtered coffee from its boiled cousin. They found that people who drank two to three cups of filtered coffee a day enjoyed a 60% lower risk of type 2 diabetes than did those who subsisted on less than one cup of filtered coffee per day. But drinking boiled coffee did nothing to dent drinkers’ diabetes risk.

Why the difference? The coffee-sipping Swedish investigators say boiled coffee contains diterpenes, which don’t make it past a coffee filter. Other studies have shown diterpenes inflate the risk of heart and vascular diseases. And the researchers say those unfiltered diterpenes may sap your morning cuppa joe’s antidiabetes powers.

We know what you’re thinking: Who boils powdered coffee? Is Sanka even a thing anymore? It’s an approach that’s unfamiliar to most Mr. Coffee–owning Scandinavians and American java junkies alike. But before you, like us, take another smug sip from that cup you just made in the Keurig machine, know this: Coffee pod machines deal out hot, unfiltered brew.

Maybe just add two sugar packets next time. Your beta cells will thank you.
 

Let my people poop!

Panama7/iStock/Getty Images Plus

This is the way the world ends, this is the way the world ends: Not with a bang, but a tilted toilet.

The latest piece of late-stage capitalistic horror comes from Great Britain, and has lovingly been called the “StandardToilet.” No dystopian overtones there, absolutely not. The toilet’s “genius” lies in the seat’s 13-degree downward slope, which increases strain on the legs just like a squat thrust would. Sit on one for more than 5 minutes, and the pain becomes too much to handle.

The inventor of the StandardToilet claims that his product will cut time employees spend on the toilet by 25%, saving businesses as much as 4.8 billion pounds sterling a year. Not only that, he suggests that there are numerous health benefits, such as reduced hemorrhoid risk and a reduction of musculoskeletal disorders.

Critics were quick to point out that people with disabilities would likely have accessibility issues (and let’s not forget people with GI diseases), and a bathroom space expert (yes, that’s a thing) suggested that, if employees are spending too much time on the toilet, the issue is likely not laziness but the poor state of affairs in the workplace itself.

As purveyors of quality toilet- and poop-themed humor, we here at Livin’ on the MDedge world headquarters think it would be a shame if the giant corporations of the world took away normal toilets. So we say to the downtrodden proletariat: Workers of the world, unite! You have nothing to lose but your toilets!
 

Livin’ on the MDedge will be taking a holiday break, but we’ll be back to advance medical science in January!

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

jremaly@mdedge.com

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

jremaly@mdedge.com

Gabapentin and pregabalin are associated with serious breathing problems when used with central nervous system depressants or in patients with lung problems, according to a Dec. 19 drug safety alert from the Food and Drug Administration. Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.

Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.

“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.

The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.

Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.

Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.

The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.

Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.

jremaly@mdedge.com

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

The Food and Drug Administration has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer that has previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy.

Enfortumab vedotin-ejfv is an antibody-drug conjugate that targets the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers.

The conjugate was approved based on overall response rate in a trial of 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the FDA said in a press statement.

The overall response rate was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.

The most common side effects for patients were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients may experience hyperglycemia, and blood sugar levels should be monitored closely in patients receiving enfortumab vedotin-ejfv, the FDA said.

Patients may experience eye disorders, and health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye, the agency said. The FDA also advises telling patients of reproductive age to use effective contraception during treatment, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take the antibody-drug conjugate because it may cause harm to a developing fetus or newborn baby or cause delivery complications.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

References

1. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156:218-226.
2. Rao VL, Micic D, Davis AM. Medical management of opioid-induced constipation. JAMA. 2019;322:2241-2242.
3. Naldemedine (Symproic) for opioid-induced constipation. Med Lett Drugs Ther. 2017;59:196-198.
4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

As the debate over how best to address surprise billing continues, new research shows that billing from out-of-network physicians at in-network facilities is adding $40 billion in costs.

utah778/Thinkstock

Researchers focused on four different types of physicians that account for out-of-network billing: anesthesiologists, pathologists, radiologists, and cases involving an assistant surgeon, which had out-of-network bills in about 10% of claims that were examined as part of the research.

“To give a rough estimate of the savings that could be achieved by eliminating the ability of these four types of specialists to readily bill out of network, we simulated what would happen if all of these specialists received the same average payments as orthopedic surgeons did (164% of Medicare rates),” Zack Cooper, PhD, associate professor of health policy at Yale University, New Haven, Conn., and colleagues wrote in a research report published in Health Affairs.

“We estimated that if these physicians were paid the same average rate as orthopedists for all of the services that they delivered in our sample, spending would be lowered on anesthesiologists by 53.5%, on pathologists by 47.4%, on radiologists by 16.3%, and on assistant surgeons by 46.2%,” the authors wrote.

Researchers said that physician spending for these four specialties would be lowered by 13.4% and would lower total spending for people with employer-sponsored insurance by about 3.4%, or $40 billion. If spending on these four specialties were lowered to 150% of Medicare rates, it would lower spending on physicians by 15.3%.

To help combat the issues of surprise billing in a way that lowers total commercial health care spending and helps to preserve a competitive price for physician services, Dr. Cooper and colleagues recommended an approach that would regulate the contracts of physicians who work in hospitals and are not chosen by patients. It would establish a bundled package for services that include the emergency department physicians and the four specialists examined as part of the research and would use the fee associated with the package of services to recruit specialists to work at the hospital.

The authors said this kind of policy would eliminate the possibility of patients seeing out-of-network providers at in-network hospitals and, unlike arbitration (a favored solution among physician groups if it is set up in an agreeable manner), patients are protected without being required to take any action. The policy also sets a competitive rate for these services.

“Under this bundled care approach, physicians would compete to offer their services on the basis of price and quality,” Dr. Cooper and colleagues stated. “Hospitals would compete with one another on the price and quality of their care, including the services provided by the physicians they recruited. Hospitals would also need to compete to retain physicians.”

This approach is not included in any current surprise billing legislation. There was hope that surprise billing would be addressed in a government spending bill that would be signed before year’s end. But a second bipartisan plan was introduced in the House Ways and Means Committee after a bipartisan compromise was reached by the House Energy and Commerce and the Senate Health, Education, Labor, and Pensions committees. This has postponed a decision on surprise billing legislation into the coming year.

gtwachtman@mdedge.com

SOURCE: Cooper Z et al. Health Aff. 2019 Dec 16. doi: 10.1377/hlthaff.2019.00507.

As the debate over how best to address surprise billing continues, new research shows that billing from out-of-network physicians at in-network facilities is adding $40 billion in costs.

utah778/Thinkstock

Researchers focused on four different types of physicians that account for out-of-network billing: anesthesiologists, pathologists, radiologists, and cases involving an assistant surgeon, which had out-of-network bills in about 10% of claims that were examined as part of the research.

“To give a rough estimate of the savings that could be achieved by eliminating the ability of these four types of specialists to readily bill out of network, we simulated what would happen if all of these specialists received the same average payments as orthopedic surgeons did (164% of Medicare rates),” Zack Cooper, PhD, associate professor of health policy at Yale University, New Haven, Conn., and colleagues wrote in a research report published in Health Affairs.

“We estimated that if these physicians were paid the same average rate as orthopedists for all of the services that they delivered in our sample, spending would be lowered on anesthesiologists by 53.5%, on pathologists by 47.4%, on radiologists by 16.3%, and on assistant surgeons by 46.2%,” the authors wrote.

Researchers said that physician spending for these four specialties would be lowered by 13.4% and would lower total spending for people with employer-sponsored insurance by about 3.4%, or $40 billion. If spending on these four specialties were lowered to 150% of Medicare rates, it would lower spending on physicians by 15.3%.

To help combat the issues of surprise billing in a way that lowers total commercial health care spending and helps to preserve a competitive price for physician services, Dr. Cooper and colleagues recommended an approach that would regulate the contracts of physicians who work in hospitals and are not chosen by patients. It would establish a bundled package for services that include the emergency department physicians and the four specialists examined as part of the research and would use the fee associated with the package of services to recruit specialists to work at the hospital.

The authors said this kind of policy would eliminate the possibility of patients seeing out-of-network providers at in-network hospitals and, unlike arbitration (a favored solution among physician groups if it is set up in an agreeable manner), patients are protected without being required to take any action. The policy also sets a competitive rate for these services.

“Under this bundled care approach, physicians would compete to offer their services on the basis of price and quality,” Dr. Cooper and colleagues stated. “Hospitals would compete with one another on the price and quality of their care, including the services provided by the physicians they recruited. Hospitals would also need to compete to retain physicians.”

This approach is not included in any current surprise billing legislation. There was hope that surprise billing would be addressed in a government spending bill that would be signed before year’s end. But a second bipartisan plan was introduced in the House Ways and Means Committee after a bipartisan compromise was reached by the House Energy and Commerce and the Senate Health, Education, Labor, and Pensions committees. This has postponed a decision on surprise billing legislation into the coming year.

gtwachtman@mdedge.com

SOURCE: Cooper Z et al. Health Aff. 2019 Dec 16. doi: 10.1377/hlthaff.2019.00507.

As the debate over how best to address surprise billing continues, new research shows that billing from out-of-network physicians at in-network facilities is adding $40 billion in costs.

utah778/Thinkstock

Researchers focused on four different types of physicians that account for out-of-network billing: anesthesiologists, pathologists, radiologists, and cases involving an assistant surgeon, which had out-of-network bills in about 10% of claims that were examined as part of the research.

“To give a rough estimate of the savings that could be achieved by eliminating the ability of these four types of specialists to readily bill out of network, we simulated what would happen if all of these specialists received the same average payments as orthopedic surgeons did (164% of Medicare rates),” Zack Cooper, PhD, associate professor of health policy at Yale University, New Haven, Conn., and colleagues wrote in a research report published in Health Affairs.

“We estimated that if these physicians were paid the same average rate as orthopedists for all of the services that they delivered in our sample, spending would be lowered on anesthesiologists by 53.5%, on pathologists by 47.4%, on radiologists by 16.3%, and on assistant surgeons by 46.2%,” the authors wrote.

Researchers said that physician spending for these four specialties would be lowered by 13.4% and would lower total spending for people with employer-sponsored insurance by about 3.4%, or $40 billion. If spending on these four specialties were lowered to 150% of Medicare rates, it would lower spending on physicians by 15.3%.

To help combat the issues of surprise billing in a way that lowers total commercial health care spending and helps to preserve a competitive price for physician services, Dr. Cooper and colleagues recommended an approach that would regulate the contracts of physicians who work in hospitals and are not chosen by patients. It would establish a bundled package for services that include the emergency department physicians and the four specialists examined as part of the research and would use the fee associated with the package of services to recruit specialists to work at the hospital.

The authors said this kind of policy would eliminate the possibility of patients seeing out-of-network providers at in-network hospitals and, unlike arbitration (a favored solution among physician groups if it is set up in an agreeable manner), patients are protected without being required to take any action. The policy also sets a competitive rate for these services.

“Under this bundled care approach, physicians would compete to offer their services on the basis of price and quality,” Dr. Cooper and colleagues stated. “Hospitals would compete with one another on the price and quality of their care, including the services provided by the physicians they recruited. Hospitals would also need to compete to retain physicians.”

This approach is not included in any current surprise billing legislation. There was hope that surprise billing would be addressed in a government spending bill that would be signed before year’s end. But a second bipartisan plan was introduced in the House Ways and Means Committee after a bipartisan compromise was reached by the House Energy and Commerce and the Senate Health, Education, Labor, and Pensions committees. This has postponed a decision on surprise billing legislation into the coming year.

gtwachtman@mdedge.com

SOURCE: Cooper Z et al. Health Aff. 2019 Dec 16. doi: 10.1377/hlthaff.2019.00507.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

SAN ANTONIO – Biofeedback for treatment of dyssynergic constipation is highly effective in the elderly, just as it is in younger patients, Samantha Spilman, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

“I think the main point of this study is that older adults have a profound burden of constipation with dyssynergic defecation, and we propose that biofeedback be given strong consideration as first-line therapy for this population, in whom overall we’re trying to reduce medication use,” said Dr. Spilman, a gastroenterology fellow at the University of California, San Diego.

The prevalence of constipation in older patients is estimated to be up to 40%. Yet few prior studies have scrutinized how well older patients with constipation actually respond to biofeedback. It’s a legitimate question, since biofeedback training involves operant conditioning and requires learning new techniques. For this reason, she and her coinvestigators conducted a retrospective analysis of 58 patients over age 65 referred from the university’s gastrointestinal motility and physiology program to the biofeedback program for treatment of dyssynergic defection. The patients’ mean age was 74 years, with a 9.5-year history of constipation. The oldest patient was 88. Most of the subjects were high school graduates. Thirteen of the 58 carried a diagnosis of irritable bowel syndrome.

Numerous studies have demonstrated that 70%-80% of younger adults with dyssynergic constipation experience marked improvement in response to biofeedback training, which typically utilizes an inflated rectal balloon to simulate retained stool. The key finding in Dr. Spilman’s study was that the elderly patients did comparably well in terms of both self-reported outcomes and objective high-resolution anorectal manometric parameters upon completing an average of three biofeedback sessions.

Mean global bowel satisfaction on a 1-10 scale nearly doubled from 2.77 at baseline to 5.01 with biofeedback. Moreover, 79% of seniors demonstrated resolution of their dyssynergia on high-resolution anorectal manometry performed with sensors in the rectum and anal canal. The proportion of patients who reported a feeling of incomplete evacuation after stooling – a sensation individuals with constipation find highly bothersome – improved from 95% to 24% with biofeedback.

The strongest response in terms of the defecation index was observed in older patients with type 2 dyssynergia, characterized by defective propulsion coupled with a paradoxical contraction of the sphincter muscles during defecation. Their defecation index score, derived by dividing intrarectal pressure by residual intra-anal pressure during simulated defection, showed a robust improvement from 0.307 at baseline to 0.793. Patients with types 1 and 3 dyssynergia showed lesser improvements on this objective measure.

Dr. Spilman noted as a study limitation that baseline cognitive status wasn’t formally assessed, so the investigators don’t know how many of the older patients had minimal cognitive impairment. However, baseline quality of life assessment via the Short Form-36 indicated that patients scored average or above for physical and social functioning as well as emotional well-being.

Dr. Spilman reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Spilman S. ACG 2019. Abstract 45.

SAN ANTONIO – Biofeedback for treatment of dyssynergic constipation is highly effective in the elderly, just as it is in younger patients, Samantha Spilman, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

“I think the main point of this study is that older adults have a profound burden of constipation with dyssynergic defecation, and we propose that biofeedback be given strong consideration as first-line therapy for this population, in whom overall we’re trying to reduce medication use,” said Dr. Spilman, a gastroenterology fellow at the University of California, San Diego.

The prevalence of constipation in older patients is estimated to be up to 40%. Yet few prior studies have scrutinized how well older patients with constipation actually respond to biofeedback. It’s a legitimate question, since biofeedback training involves operant conditioning and requires learning new techniques. For this reason, she and her coinvestigators conducted a retrospective analysis of 58 patients over age 65 referred from the university’s gastrointestinal motility and physiology program to the biofeedback program for treatment of dyssynergic defection. The patients’ mean age was 74 years, with a 9.5-year history of constipation. The oldest patient was 88. Most of the subjects were high school graduates. Thirteen of the 58 carried a diagnosis of irritable bowel syndrome.

Numerous studies have demonstrated that 70%-80% of younger adults with dyssynergic constipation experience marked improvement in response to biofeedback training, which typically utilizes an inflated rectal balloon to simulate retained stool. The key finding in Dr. Spilman’s study was that the elderly patients did comparably well in terms of both self-reported outcomes and objective high-resolution anorectal manometric parameters upon completing an average of three biofeedback sessions.

Mean global bowel satisfaction on a 1-10 scale nearly doubled from 2.77 at baseline to 5.01 with biofeedback. Moreover, 79% of seniors demonstrated resolution of their dyssynergia on high-resolution anorectal manometry performed with sensors in the rectum and anal canal. The proportion of patients who reported a feeling of incomplete evacuation after stooling – a sensation individuals with constipation find highly bothersome – improved from 95% to 24% with biofeedback.

The strongest response in terms of the defecation index was observed in older patients with type 2 dyssynergia, characterized by defective propulsion coupled with a paradoxical contraction of the sphincter muscles during defecation. Their defecation index score, derived by dividing intrarectal pressure by residual intra-anal pressure during simulated defection, showed a robust improvement from 0.307 at baseline to 0.793. Patients with types 1 and 3 dyssynergia showed lesser improvements on this objective measure.

Dr. Spilman noted as a study limitation that baseline cognitive status wasn’t formally assessed, so the investigators don’t know how many of the older patients had minimal cognitive impairment. However, baseline quality of life assessment via the Short Form-36 indicated that patients scored average or above for physical and social functioning as well as emotional well-being.

Dr. Spilman reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Spilman S. ACG 2019. Abstract 45.

SAN ANTONIO – Biofeedback for treatment of dyssynergic constipation is highly effective in the elderly, just as it is in younger patients, Samantha Spilman, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

“I think the main point of this study is that older adults have a profound burden of constipation with dyssynergic defecation, and we propose that biofeedback be given strong consideration as first-line therapy for this population, in whom overall we’re trying to reduce medication use,” said Dr. Spilman, a gastroenterology fellow at the University of California, San Diego.

The prevalence of constipation in older patients is estimated to be up to 40%. Yet few prior studies have scrutinized how well older patients with constipation actually respond to biofeedback. It’s a legitimate question, since biofeedback training involves operant conditioning and requires learning new techniques. For this reason, she and her coinvestigators conducted a retrospective analysis of 58 patients over age 65 referred from the university’s gastrointestinal motility and physiology program to the biofeedback program for treatment of dyssynergic defection. The patients’ mean age was 74 years, with a 9.5-year history of constipation. The oldest patient was 88. Most of the subjects were high school graduates. Thirteen of the 58 carried a diagnosis of irritable bowel syndrome.

Numerous studies have demonstrated that 70%-80% of younger adults with dyssynergic constipation experience marked improvement in response to biofeedback training, which typically utilizes an inflated rectal balloon to simulate retained stool. The key finding in Dr. Spilman’s study was that the elderly patients did comparably well in terms of both self-reported outcomes and objective high-resolution anorectal manometric parameters upon completing an average of three biofeedback sessions.

Mean global bowel satisfaction on a 1-10 scale nearly doubled from 2.77 at baseline to 5.01 with biofeedback. Moreover, 79% of seniors demonstrated resolution of their dyssynergia on high-resolution anorectal manometry performed with sensors in the rectum and anal canal. The proportion of patients who reported a feeling of incomplete evacuation after stooling – a sensation individuals with constipation find highly bothersome – improved from 95% to 24% with biofeedback.

The strongest response in terms of the defecation index was observed in older patients with type 2 dyssynergia, characterized by defective propulsion coupled with a paradoxical contraction of the sphincter muscles during defecation. Their defecation index score, derived by dividing intrarectal pressure by residual intra-anal pressure during simulated defection, showed a robust improvement from 0.307 at baseline to 0.793. Patients with types 1 and 3 dyssynergia showed lesser improvements on this objective measure.

Dr. Spilman noted as a study limitation that baseline cognitive status wasn’t formally assessed, so the investigators don’t know how many of the older patients had minimal cognitive impairment. However, baseline quality of life assessment via the Short Form-36 indicated that patients scored average or above for physical and social functioning as well as emotional well-being.

Dr. Spilman reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Spilman S. ACG 2019. Abstract 45.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

BALTIMORE – Investigators from the University of California, San Francisco, are working with medical directors across the state to update county emergency medical services protocols to ensure patients in status epilepticus get 10 mg IM midazolam in the field, per national treatment guidelines from the American Epilepsy Society.

The work comes in the wake of a recent research letter in JAMA where the UCSF team reported that, across 33 emergency medical services (EMS) in California, only 2 included 10 mg midazolam IM per the guidelines, advice based on randomized, controlled clinical trials that found it to be safe and effective for stopping prehospital seizures in adults.

“Making people aware of the problem [is having] an impact,” said investigator Elan Guterman, MD, a neurology hospitalist and assistant professor of neurology at the university.

In a follow-up review at the annual meeting of the American Epilepsy Society, the team took a deep dive into the situation in Alameda County, just east of San Francisco and including the city of Oakland, as an indicator of what’s been going on across the state.

Patients had to have an EMS record of active seizures, meaning more than two within 5 minutes or a single seizure lasting more than 5 minutes. Alameda ambulance crews, like most, carry intramuscular midazolam because it’s more shelf stable than the two other first-line options, lorazepam and diazepam, and doesn’t require an intravenous line.

Among the 2,494 adults treated for status epilepticus from 2013 to 2018, just 62% received intramuscular midazolam, and only 39% got a dose of 5 mg or more. Not a single patient received the recommended 10-mg IM injection.

In short, “at the time when it’s the most important to act quickly, patients were not receiving the care they needed,” and the problem isn’t likely limited to California, Dr. Guterman said.

When patients did get 5 mg or more, they were less likely to reseize and require additional doses (adjusted odds ratio, 0.59; 95% CI, 0.4-0.86). Also – and counterintuitively given the concern about benzodiazepines and respiratory depression – the team found that higher initial doses of 5 mg or more were actually associated with a lower need for respiratory support, including intubation (OR, 0.81; 95% CI, 0.67-0.99).

It’s possible ambulance crews were erring on the side of caution. People who got midazolam were more likely to have an established diagnosis of epilepsy (68% vs. 62%; P less than .01) and less likely to have been abusing drugs or alcohol (12.5% vs. 16.3%; P less than .01).

But an abundance of caution doesn’t fully explain it; even among people known to have epilepsy, many weren’t treated with midazolam and none at the appropriate dose.

Dr. Guterman thinks the bigger issue is what was reported in the research letter: Local EMS protocols simply haven’t been updated to include current best practices. EMS services might not even be aware of them, which is why she and her colleagues have been meeting with county medical directors.

“The first step is making sure the EMS world is aware of this gap in care, and motivating them to address it,” she said.

Patients in the study were a mean of 53 years old, and just over half were men.

There was no industry funding for the study, and Dr. Guterman didn’t report any relevant disclosures.

aotto@mdedge.com

SOURCE: Guterman E et al. AES 2019, Abstract 1.394.

BALTIMORE – Investigators from the University of California, San Francisco, are working with medical directors across the state to update county emergency medical services protocols to ensure patients in status epilepticus get 10 mg IM midazolam in the field, per national treatment guidelines from the American Epilepsy Society.

The work comes in the wake of a recent research letter in JAMA where the UCSF team reported that, across 33 emergency medical services (EMS) in California, only 2 included 10 mg midazolam IM per the guidelines, advice based on randomized, controlled clinical trials that found it to be safe and effective for stopping prehospital seizures in adults.

“Making people aware of the problem [is having] an impact,” said investigator Elan Guterman, MD, a neurology hospitalist and assistant professor of neurology at the university.

In a follow-up review at the annual meeting of the American Epilepsy Society, the team took a deep dive into the situation in Alameda County, just east of San Francisco and including the city of Oakland, as an indicator of what’s been going on across the state.

Patients had to have an EMS record of active seizures, meaning more than two within 5 minutes or a single seizure lasting more than 5 minutes. Alameda ambulance crews, like most, carry intramuscular midazolam because it’s more shelf stable than the two other first-line options, lorazepam and diazepam, and doesn’t require an intravenous line.

Among the 2,494 adults treated for status epilepticus from 2013 to 2018, just 62% received intramuscular midazolam, and only 39% got a dose of 5 mg or more. Not a single patient received the recommended 10-mg IM injection.

In short, “at the time when it’s the most important to act quickly, patients were not receiving the care they needed,” and the problem isn’t likely limited to California, Dr. Guterman said.

When patients did get 5 mg or more, they were less likely to reseize and require additional doses (adjusted odds ratio, 0.59; 95% CI, 0.4-0.86). Also – and counterintuitively given the concern about benzodiazepines and respiratory depression – the team found that higher initial doses of 5 mg or more were actually associated with a lower need for respiratory support, including intubation (OR, 0.81; 95% CI, 0.67-0.99).

It’s possible ambulance crews were erring on the side of caution. People who got midazolam were more likely to have an established diagnosis of epilepsy (68% vs. 62%; P less than .01) and less likely to have been abusing drugs or alcohol (12.5% vs. 16.3%; P less than .01).

But an abundance of caution doesn’t fully explain it; even among people known to have epilepsy, many weren’t treated with midazolam and none at the appropriate dose.

Dr. Guterman thinks the bigger issue is what was reported in the research letter: Local EMS protocols simply haven’t been updated to include current best practices. EMS services might not even be aware of them, which is why she and her colleagues have been meeting with county medical directors.

“The first step is making sure the EMS world is aware of this gap in care, and motivating them to address it,” she said.

Patients in the study were a mean of 53 years old, and just over half were men.

There was no industry funding for the study, and Dr. Guterman didn’t report any relevant disclosures.

aotto@mdedge.com

SOURCE: Guterman E et al. AES 2019, Abstract 1.394.

BALTIMORE – Investigators from the University of California, San Francisco, are working with medical directors across the state to update county emergency medical services protocols to ensure patients in status epilepticus get 10 mg IM midazolam in the field, per national treatment guidelines from the American Epilepsy Society.

The work comes in the wake of a recent research letter in JAMA where the UCSF team reported that, across 33 emergency medical services (EMS) in California, only 2 included 10 mg midazolam IM per the guidelines, advice based on randomized, controlled clinical trials that found it to be safe and effective for stopping prehospital seizures in adults.

“Making people aware of the problem [is having] an impact,” said investigator Elan Guterman, MD, a neurology hospitalist and assistant professor of neurology at the university.

In a follow-up review at the annual meeting of the American Epilepsy Society, the team took a deep dive into the situation in Alameda County, just east of San Francisco and including the city of Oakland, as an indicator of what’s been going on across the state.

Patients had to have an EMS record of active seizures, meaning more than two within 5 minutes or a single seizure lasting more than 5 minutes. Alameda ambulance crews, like most, carry intramuscular midazolam because it’s more shelf stable than the two other first-line options, lorazepam and diazepam, and doesn’t require an intravenous line.

Among the 2,494 adults treated for status epilepticus from 2013 to 2018, just 62% received intramuscular midazolam, and only 39% got a dose of 5 mg or more. Not a single patient received the recommended 10-mg IM injection.

In short, “at the time when it’s the most important to act quickly, patients were not receiving the care they needed,” and the problem isn’t likely limited to California, Dr. Guterman said.

When patients did get 5 mg or more, they were less likely to reseize and require additional doses (adjusted odds ratio, 0.59; 95% CI, 0.4-0.86). Also – and counterintuitively given the concern about benzodiazepines and respiratory depression – the team found that higher initial doses of 5 mg or more were actually associated with a lower need for respiratory support, including intubation (OR, 0.81; 95% CI, 0.67-0.99).

It’s possible ambulance crews were erring on the side of caution. People who got midazolam were more likely to have an established diagnosis of epilepsy (68% vs. 62%; P less than .01) and less likely to have been abusing drugs or alcohol (12.5% vs. 16.3%; P less than .01).

But an abundance of caution doesn’t fully explain it; even among people known to have epilepsy, many weren’t treated with midazolam and none at the appropriate dose.

Dr. Guterman thinks the bigger issue is what was reported in the research letter: Local EMS protocols simply haven’t been updated to include current best practices. EMS services might not even be aware of them, which is why she and her colleagues have been meeting with county medical directors.

“The first step is making sure the EMS world is aware of this gap in care, and motivating them to address it,” she said.

Patients in the study were a mean of 53 years old, and just over half were men.

There was no industry funding for the study, and Dr. Guterman didn’t report any relevant disclosures.

aotto@mdedge.com

SOURCE: Guterman E et al. AES 2019, Abstract 1.394.