The European League Against Rheumatism’s updated recommendations on gout generally resemble those from the American College of Rheumatology, but with several important caveats, two prominent U.S. rheumatologists said in interviews.

First came the praise. “Both ACR and EULAR are sending a consistent message that gout needs more attention and improvement in the quality of care that’s being provided,” said John FitzGerald, MD, PhD, who coauthored the 2012 ACR guidelines and is a professor of medicine and rheumatology at the University of California, Los Angeles.

EULAR also strengthened its advice to start urate-lowering therapy (ULT) early (Ann Rheum Dis. 2016 Jul 25. doi: 10.1136/annrheumdis-2016-209707). This choice reflects “the opinion of many gout experts, that delaying treatment only allows for further accumulation of monosodium urate deposition around the body, which promotes inflammation and tissue destruction and makes it harder to achieve clinical and biologic remission,” said N. Lawrence Edwards, MD, who also helped write the ACR guidelines and is a vice chairman of the department of medicine at the University of Florida, Gainesville.

Finally, EULAR again emphasized treating to a target serum urate level of less than 6.0 mg/dL. “That is definitely consistent with the current recommendations from ACR, and with the way most rheumatologists think,” Dr. FitzGerald said. “The recommendations for future research are also very good and should be commended.”

But several other points depart from the ACR guidance and have prompted critiques.

Allopurinol

Perhaps most strikingly, EULAR now recommends adjusting maximum allopurinol dose based on creatinine clearance if patients have renal impairment. “This modification is very surprising, since [it has] never been shown to affect the incidence of severe allopurinol hypersensitivity reactions,” Dr. Edwards said. “Instead, these antiquated treatment schedules have only added to the epidemic of underdosing of allopurinol by both general practitioners and rheumatologists alike.”

Indeed, requiring clinicians to consider creatinine clearance when using allopurinol in many of their gout patients might push them toward other drugs and their accompanying side effects, “without first trying a slow, safe titration” of allopurinol, Dr. FitzGerald said.

Instead, both he and Dr. Edwards recommended following the gradual allopurinol dose escalation detailed in the 2012 ACR recommendations. “The biggest risk of adverse effects with allopurinol is during the initial treatment period, whereas there is little data about maximum dose,” Dr. FitzGerald emphasized. “I think the starting dose should be 50 mg every day, or even 50 mg every other day – the latter if patients have stage 4 chronic kidney disease.”

Serum urate

EULAR also advises against letting serum urate fall below 3.0 mg/dL “in the long term” – that is, over several years. This guidance stems from reports that hyperuricemia could help prevent neurodegenerative diseases, Dr. Edwards said. But studies have never clearly linked serum urate to neurologic processes, nor have they shown that low serum urate triggers or worsens disease, he added. “The harm of this EULAR recommendation comes from the chilling effect it might have on getting internists and general practitioners to more fully engage in urate lowering in subjects with gout. They could view a therapeutic serum urate window of 3.0 mg/dL to 6.0 mg/dL as too narrow and requiring too much oversight – leading once again to undertreatment.”

Comorbidities

ACR already had recommended ULT for gout patients with chronic kidney disease or urate renoliths, but EULAR expanded this list to include not only renal impairment, but also hypertension, ischemic heart disease, and heart failure, Dr. FitzGerald pointed out. “The recommendation for hypertension was based on a systematic literature review, but hypertension is so prevalent that this additional recommendation really expands the number of patients that would be treated with ULT,” he added. “If it is a patient’s first attack of gout, I think a lot of primary care providers would be uncomfortable starting patients on ULT.”

EULAR and ACR have always diverged in their recommendations about who should receive ULT, and widening these criteria further without direct supporting evidence from a clinical trial will provoke concerns, according to Dr. FitzGerald. “The EULAR authors lay out the logic for it, but without direct evidence it will be controversial, and the risk-benefit ratio of treating this expanded list of patients is unclear.”

Febuxostat

Dr. FitzGerald also recommended starting the xanthine oxidase inhibitor febuxostat (Uloric) at 40 mg, rather than 80 mg as recommended by EULAR. “This is based on a similar logic, that starting lower and titrating up has less risks than starting at a higher dose.”

Dr. Pascal Richette, first author of the updated EULAR recommendations, disclosed fees from Ipsen Pharma/Menarini, AstraZeneca, and Savient. Dr. FitzGerald and Dr. Edwards were coauthors of the 2012 ACR guidelines on gout, part 1 and part 2.

The European League Against Rheumatism’s updated recommendations on gout generally resemble those from the American College of Rheumatology, but with several important caveats, two prominent U.S. rheumatologists said in interviews.

First came the praise. “Both ACR and EULAR are sending a consistent message that gout needs more attention and improvement in the quality of care that’s being provided,” said John FitzGerald, MD, PhD, who coauthored the 2012 ACR guidelines and is a professor of medicine and rheumatology at the University of California, Los Angeles.

EULAR also strengthened its advice to start urate-lowering therapy (ULT) early (Ann Rheum Dis. 2016 Jul 25. doi: 10.1136/annrheumdis-2016-209707). This choice reflects “the opinion of many gout experts, that delaying treatment only allows for further accumulation of monosodium urate deposition around the body, which promotes inflammation and tissue destruction and makes it harder to achieve clinical and biologic remission,” said N. Lawrence Edwards, MD, who also helped write the ACR guidelines and is a vice chairman of the department of medicine at the University of Florida, Gainesville.

Finally, EULAR again emphasized treating to a target serum urate level of less than 6.0 mg/dL. “That is definitely consistent with the current recommendations from ACR, and with the way most rheumatologists think,” Dr. FitzGerald said. “The recommendations for future research are also very good and should be commended.”

But several other points depart from the ACR guidance and have prompted critiques.

Allopurinol

Perhaps most strikingly, EULAR now recommends adjusting maximum allopurinol dose based on creatinine clearance if patients have renal impairment. “This modification is very surprising, since [it has] never been shown to affect the incidence of severe allopurinol hypersensitivity reactions,” Dr. Edwards said. “Instead, these antiquated treatment schedules have only added to the epidemic of underdosing of allopurinol by both general practitioners and rheumatologists alike.”

Indeed, requiring clinicians to consider creatinine clearance when using allopurinol in many of their gout patients might push them toward other drugs and their accompanying side effects, “without first trying a slow, safe titration” of allopurinol, Dr. FitzGerald said.

Instead, both he and Dr. Edwards recommended following the gradual allopurinol dose escalation detailed in the 2012 ACR recommendations. “The biggest risk of adverse effects with allopurinol is during the initial treatment period, whereas there is little data about maximum dose,” Dr. FitzGerald emphasized. “I think the starting dose should be 50 mg every day, or even 50 mg every other day – the latter if patients have stage 4 chronic kidney disease.”

Serum urate

EULAR also advises against letting serum urate fall below 3.0 mg/dL “in the long term” – that is, over several years. This guidance stems from reports that hyperuricemia could help prevent neurodegenerative diseases, Dr. Edwards said. But studies have never clearly linked serum urate to neurologic processes, nor have they shown that low serum urate triggers or worsens disease, he added. “The harm of this EULAR recommendation comes from the chilling effect it might have on getting internists and general practitioners to more fully engage in urate lowering in subjects with gout. They could view a therapeutic serum urate window of 3.0 mg/dL to 6.0 mg/dL as too narrow and requiring too much oversight – leading once again to undertreatment.”

Comorbidities

ACR already had recommended ULT for gout patients with chronic kidney disease or urate renoliths, but EULAR expanded this list to include not only renal impairment, but also hypertension, ischemic heart disease, and heart failure, Dr. FitzGerald pointed out. “The recommendation for hypertension was based on a systematic literature review, but hypertension is so prevalent that this additional recommendation really expands the number of patients that would be treated with ULT,” he added. “If it is a patient’s first attack of gout, I think a lot of primary care providers would be uncomfortable starting patients on ULT.”

EULAR and ACR have always diverged in their recommendations about who should receive ULT, and widening these criteria further without direct supporting evidence from a clinical trial will provoke concerns, according to Dr. FitzGerald. “The EULAR authors lay out the logic for it, but without direct evidence it will be controversial, and the risk-benefit ratio of treating this expanded list of patients is unclear.”

Febuxostat

Dr. FitzGerald also recommended starting the xanthine oxidase inhibitor febuxostat (Uloric) at 40 mg, rather than 80 mg as recommended by EULAR. “This is based on a similar logic, that starting lower and titrating up has less risks than starting at a higher dose.”

Dr. Pascal Richette, first author of the updated EULAR recommendations, disclosed fees from Ipsen Pharma/Menarini, AstraZeneca, and Savient. Dr. FitzGerald and Dr. Edwards were coauthors of the 2012 ACR guidelines on gout, part 1 and part 2.

The European League Against Rheumatism’s updated recommendations on gout generally resemble those from the American College of Rheumatology, but with several important caveats, two prominent U.S. rheumatologists said in interviews.

First came the praise. “Both ACR and EULAR are sending a consistent message that gout needs more attention and improvement in the quality of care that’s being provided,” said John FitzGerald, MD, PhD, who coauthored the 2012 ACR guidelines and is a professor of medicine and rheumatology at the University of California, Los Angeles.

EULAR also strengthened its advice to start urate-lowering therapy (ULT) early (Ann Rheum Dis. 2016 Jul 25. doi: 10.1136/annrheumdis-2016-209707). This choice reflects “the opinion of many gout experts, that delaying treatment only allows for further accumulation of monosodium urate deposition around the body, which promotes inflammation and tissue destruction and makes it harder to achieve clinical and biologic remission,” said N. Lawrence Edwards, MD, who also helped write the ACR guidelines and is a vice chairman of the department of medicine at the University of Florida, Gainesville.

Finally, EULAR again emphasized treating to a target serum urate level of less than 6.0 mg/dL. “That is definitely consistent with the current recommendations from ACR, and with the way most rheumatologists think,” Dr. FitzGerald said. “The recommendations for future research are also very good and should be commended.”

But several other points depart from the ACR guidance and have prompted critiques.

Allopurinol

Perhaps most strikingly, EULAR now recommends adjusting maximum allopurinol dose based on creatinine clearance if patients have renal impairment. “This modification is very surprising, since [it has] never been shown to affect the incidence of severe allopurinol hypersensitivity reactions,” Dr. Edwards said. “Instead, these antiquated treatment schedules have only added to the epidemic of underdosing of allopurinol by both general practitioners and rheumatologists alike.”

Indeed, requiring clinicians to consider creatinine clearance when using allopurinol in many of their gout patients might push them toward other drugs and their accompanying side effects, “without first trying a slow, safe titration” of allopurinol, Dr. FitzGerald said.

Instead, both he and Dr. Edwards recommended following the gradual allopurinol dose escalation detailed in the 2012 ACR recommendations. “The biggest risk of adverse effects with allopurinol is during the initial treatment period, whereas there is little data about maximum dose,” Dr. FitzGerald emphasized. “I think the starting dose should be 50 mg every day, or even 50 mg every other day – the latter if patients have stage 4 chronic kidney disease.”

Serum urate

EULAR also advises against letting serum urate fall below 3.0 mg/dL “in the long term” – that is, over several years. This guidance stems from reports that hyperuricemia could help prevent neurodegenerative diseases, Dr. Edwards said. But studies have never clearly linked serum urate to neurologic processes, nor have they shown that low serum urate triggers or worsens disease, he added. “The harm of this EULAR recommendation comes from the chilling effect it might have on getting internists and general practitioners to more fully engage in urate lowering in subjects with gout. They could view a therapeutic serum urate window of 3.0 mg/dL to 6.0 mg/dL as too narrow and requiring too much oversight – leading once again to undertreatment.”

Comorbidities

ACR already had recommended ULT for gout patients with chronic kidney disease or urate renoliths, but EULAR expanded this list to include not only renal impairment, but also hypertension, ischemic heart disease, and heart failure, Dr. FitzGerald pointed out. “The recommendation for hypertension was based on a systematic literature review, but hypertension is so prevalent that this additional recommendation really expands the number of patients that would be treated with ULT,” he added. “If it is a patient’s first attack of gout, I think a lot of primary care providers would be uncomfortable starting patients on ULT.”

EULAR and ACR have always diverged in their recommendations about who should receive ULT, and widening these criteria further without direct supporting evidence from a clinical trial will provoke concerns, according to Dr. FitzGerald. “The EULAR authors lay out the logic for it, but without direct evidence it will be controversial, and the risk-benefit ratio of treating this expanded list of patients is unclear.”

Febuxostat

Dr. FitzGerald also recommended starting the xanthine oxidase inhibitor febuxostat (Uloric) at 40 mg, rather than 80 mg as recommended by EULAR. “This is based on a similar logic, that starting lower and titrating up has less risks than starting at a higher dose.”

Dr. Pascal Richette, first author of the updated EULAR recommendations, disclosed fees from Ipsen Pharma/Menarini, AstraZeneca, and Savient. Dr. FitzGerald and Dr. Edwards were coauthors of the 2012 ACR guidelines on gout, part 1 and part 2.

Speaker: Lisa Zaoutis, MD, Pediatric Residency Program Director at the Children’s Hospital of Philadelphia.

Amid the skyscrapers of the Windy City, Pediatric Hospital Medicine (PHM) 2016 swept into town, bringing with it the denizens of pediatric hospitalist programs across the country. Some 1,150 attendees, comprised of hospitalists, PHM program leaders, and advanced care practitioners, gathered to educate and inspire one another in the the care of hospitalized children.

Dr. Lisa Zaoutis, director of the pediatric residency program at Children’s Hospital of Philadelphia, kicked off the conference with the opening plenary. Initially titled “North Star and Space,” she quickly changed the title to, “Changing Our Minds.” Touching on the disconnect between positive experiences that bring physicians into PHM and negative experiences that often drive behavior, she started with the beginning, the evolution of our brains.

“We are wired toward the negative,” stated Dr. Zaoutis. “We are Teflon for positive experiences and Velcro for negative experiences.” In addition, negative experiences are more likely to be stored in our memories. “It’s easy to park negative experiences.”

Delving deeper into neuroanatomy, Dr. Zaoutis spoke of “amygdala hijack,” where chronic stress inherent to the professional lives of pediatric hospitalists lead to anxiety responses that are faster, more robust, and triggered more easily.

But all is not lost, asserted Dr. Zaoutis, as our brains are more plastic than previously known. The “neural Darwinism,” of our brains, as Dr. Zaoutis states, leads to epigenetic intracellular changes, more sensitive synapses, improved blood flow, and even new cells as a result of experience dependent neuroplasticity. For example, stated Dr. Zaoutis, London taxi drivers have thicker white matter in their hippocampus as a result of the effect of learning London city streets, and mindfulness meditators have thicker gray matter in regions that control attention and self-insight.

Key Takeaways:

The lesson for pediatric hospitalists, stated Dr. Zaoutis, is that you can shape your brain for greater joy. “Consciously choose activities,” said Dr. Zaoutis, that counter our evolutionary negativity bias. How is this done?

1. Have a positive experience (you can create one or retrieve a prior one);

2. Enrich it and install it by dwelling on it for at least 15-30 seconds; and

3. Absorb it into your body, which my require somatisizing it – Dr. Zaoutis presses her hand into her chest to aid in this.

Further, spread this to your group by the old medical training technique of “see one, do one, teach one.” See if you can start your signout with the best thing that happened to you in the week. Most importantly, start with observing yourself.

Speaker: Lisa Zaoutis, MD, Pediatric Residency Program Director at the Children’s Hospital of Philadelphia.

Amid the skyscrapers of the Windy City, Pediatric Hospital Medicine (PHM) 2016 swept into town, bringing with it the denizens of pediatric hospitalist programs across the country. Some 1,150 attendees, comprised of hospitalists, PHM program leaders, and advanced care practitioners, gathered to educate and inspire one another in the the care of hospitalized children.

Dr. Lisa Zaoutis, director of the pediatric residency program at Children’s Hospital of Philadelphia, kicked off the conference with the opening plenary. Initially titled “North Star and Space,” she quickly changed the title to, “Changing Our Minds.” Touching on the disconnect between positive experiences that bring physicians into PHM and negative experiences that often drive behavior, she started with the beginning, the evolution of our brains.

“We are wired toward the negative,” stated Dr. Zaoutis. “We are Teflon for positive experiences and Velcro for negative experiences.” In addition, negative experiences are more likely to be stored in our memories. “It’s easy to park negative experiences.”

Delving deeper into neuroanatomy, Dr. Zaoutis spoke of “amygdala hijack,” where chronic stress inherent to the professional lives of pediatric hospitalists lead to anxiety responses that are faster, more robust, and triggered more easily.

But all is not lost, asserted Dr. Zaoutis, as our brains are more plastic than previously known. The “neural Darwinism,” of our brains, as Dr. Zaoutis states, leads to epigenetic intracellular changes, more sensitive synapses, improved blood flow, and even new cells as a result of experience dependent neuroplasticity. For example, stated Dr. Zaoutis, London taxi drivers have thicker white matter in their hippocampus as a result of the effect of learning London city streets, and mindfulness meditators have thicker gray matter in regions that control attention and self-insight.

Key Takeaways:

The lesson for pediatric hospitalists, stated Dr. Zaoutis, is that you can shape your brain for greater joy. “Consciously choose activities,” said Dr. Zaoutis, that counter our evolutionary negativity bias. How is this done?

1. Have a positive experience (you can create one or retrieve a prior one);

2. Enrich it and install it by dwelling on it for at least 15-30 seconds; and

3. Absorb it into your body, which my require somatisizing it – Dr. Zaoutis presses her hand into her chest to aid in this.

Further, spread this to your group by the old medical training technique of “see one, do one, teach one.” See if you can start your signout with the best thing that happened to you in the week. Most importantly, start with observing yourself.

Speaker: Lisa Zaoutis, MD, Pediatric Residency Program Director at the Children’s Hospital of Philadelphia.

Amid the skyscrapers of the Windy City, Pediatric Hospital Medicine (PHM) 2016 swept into town, bringing with it the denizens of pediatric hospitalist programs across the country. Some 1,150 attendees, comprised of hospitalists, PHM program leaders, and advanced care practitioners, gathered to educate and inspire one another in the the care of hospitalized children.

Dr. Lisa Zaoutis, director of the pediatric residency program at Children’s Hospital of Philadelphia, kicked off the conference with the opening plenary. Initially titled “North Star and Space,” she quickly changed the title to, “Changing Our Minds.” Touching on the disconnect between positive experiences that bring physicians into PHM and negative experiences that often drive behavior, she started with the beginning, the evolution of our brains.

“We are wired toward the negative,” stated Dr. Zaoutis. “We are Teflon for positive experiences and Velcro for negative experiences.” In addition, negative experiences are more likely to be stored in our memories. “It’s easy to park negative experiences.”

Delving deeper into neuroanatomy, Dr. Zaoutis spoke of “amygdala hijack,” where chronic stress inherent to the professional lives of pediatric hospitalists lead to anxiety responses that are faster, more robust, and triggered more easily.

But all is not lost, asserted Dr. Zaoutis, as our brains are more plastic than previously known. The “neural Darwinism,” of our brains, as Dr. Zaoutis states, leads to epigenetic intracellular changes, more sensitive synapses, improved blood flow, and even new cells as a result of experience dependent neuroplasticity. For example, stated Dr. Zaoutis, London taxi drivers have thicker white matter in their hippocampus as a result of the effect of learning London city streets, and mindfulness meditators have thicker gray matter in regions that control attention and self-insight.

Key Takeaways:

The lesson for pediatric hospitalists, stated Dr. Zaoutis, is that you can shape your brain for greater joy. “Consciously choose activities,” said Dr. Zaoutis, that counter our evolutionary negativity bias. How is this done?

1. Have a positive experience (you can create one or retrieve a prior one);

2. Enrich it and install it by dwelling on it for at least 15-30 seconds; and

3. Absorb it into your body, which my require somatisizing it – Dr. Zaoutis presses her hand into her chest to aid in this.

Further, spread this to your group by the old medical training technique of “see one, do one, teach one.” See if you can start your signout with the best thing that happened to you in the week. Most importantly, start with observing yourself.

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com

Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.

“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).

©KatarzynaBialasiewicz/ Thinkstock.com

Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.

Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.

Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.

However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.

Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”

Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com

Older age at the time of autism spectrum disorder diagnosis was associated with a higher likelihood of psychotropic medication in children aged 6-11, according to Katharine Zuckerman, MD, and her associates.

The mean age at diagnosis for the 722 children included in the study was 4.4 years, with a mean diagnostic delay of 2.2 years. The adjusted odds ratio for psychotropic drug use in children who were diagnosed with autism spectrum disorder (ASD) after the age of 4 was 3.09, compared with children diagnosed before the age of 4. Children diagnosed at a later age were less likely to receive behavioral intervention (BI) therapy (adjusted odds ratio = 0.44), complementary and alternative medicine (aOR = 0.63), and school-based therapy (aOR = 0.38).

©roobcio/thinkstockphotos.com

Children who experienced at least 2 years of delay before diagnosis were also significantly more likely to use psychotropic drugs (aOR = 1.77), and less likely to receive BI therapy (aOR = 0.54) and school-based therapy (aOR = 0.59). However, a delay of at least 2 years was associated with a greater chance of receiving complementary and alternative medicine (aOR = 2.81).

“Results suggest that if long-term ASD therapy use is a priority, payers and policymakers may need to proactively accelerate diagnosis by incentivizing screening or enhancing case management of children at high risk of diagnostic delays. From a population standpoint, as children receive earlier ASD diagnoses, payers may expect changes in service use patterns toward more therapy use and less pharmacology,” the investigators wrote.

Find the full study online in Psychiatric Services (doi:10.1176/appi.ps.201500549).

lfranki@frontlinemedcom.com

Older age at the time of autism spectrum disorder diagnosis was associated with a higher likelihood of psychotropic medication in children aged 6-11, according to Katharine Zuckerman, MD, and her associates.

The mean age at diagnosis for the 722 children included in the study was 4.4 years, with a mean diagnostic delay of 2.2 years. The adjusted odds ratio for psychotropic drug use in children who were diagnosed with autism spectrum disorder (ASD) after the age of 4 was 3.09, compared with children diagnosed before the age of 4. Children diagnosed at a later age were less likely to receive behavioral intervention (BI) therapy (adjusted odds ratio = 0.44), complementary and alternative medicine (aOR = 0.63), and school-based therapy (aOR = 0.38).

©roobcio/thinkstockphotos.com

Children who experienced at least 2 years of delay before diagnosis were also significantly more likely to use psychotropic drugs (aOR = 1.77), and less likely to receive BI therapy (aOR = 0.54) and school-based therapy (aOR = 0.59). However, a delay of at least 2 years was associated with a greater chance of receiving complementary and alternative medicine (aOR = 2.81).

“Results suggest that if long-term ASD therapy use is a priority, payers and policymakers may need to proactively accelerate diagnosis by incentivizing screening or enhancing case management of children at high risk of diagnostic delays. From a population standpoint, as children receive earlier ASD diagnoses, payers may expect changes in service use patterns toward more therapy use and less pharmacology,” the investigators wrote.

Find the full study online in Psychiatric Services (doi:10.1176/appi.ps.201500549).

lfranki@frontlinemedcom.com

Older age at the time of autism spectrum disorder diagnosis was associated with a higher likelihood of psychotropic medication in children aged 6-11, according to Katharine Zuckerman, MD, and her associates.

The mean age at diagnosis for the 722 children included in the study was 4.4 years, with a mean diagnostic delay of 2.2 years. The adjusted odds ratio for psychotropic drug use in children who were diagnosed with autism spectrum disorder (ASD) after the age of 4 was 3.09, compared with children diagnosed before the age of 4. Children diagnosed at a later age were less likely to receive behavioral intervention (BI) therapy (adjusted odds ratio = 0.44), complementary and alternative medicine (aOR = 0.63), and school-based therapy (aOR = 0.38).

©roobcio/thinkstockphotos.com

Children who experienced at least 2 years of delay before diagnosis were also significantly more likely to use psychotropic drugs (aOR = 1.77), and less likely to receive BI therapy (aOR = 0.54) and school-based therapy (aOR = 0.59). However, a delay of at least 2 years was associated with a greater chance of receiving complementary and alternative medicine (aOR = 2.81).

“Results suggest that if long-term ASD therapy use is a priority, payers and policymakers may need to proactively accelerate diagnosis by incentivizing screening or enhancing case management of children at high risk of diagnostic delays. From a population standpoint, as children receive earlier ASD diagnoses, payers may expect changes in service use patterns toward more therapy use and less pharmacology,” the investigators wrote.

Find the full study online in Psychiatric Services (doi:10.1176/appi.ps.201500549).

lfranki@frontlinemedcom.com

Buy our EHR. Come to a dinner and see our EHR. Our EHR is the best.

I hear that a lot, but am not rushing out to get one. Yes, I have an EHR, but it’s one I designed myself. It works very well for my dinky little practice, and I’m happy with it.

I get notes from practices that use commercial EHRs all the time. They’re usually a pile of gobbledygook, mixing labs, vital signs, medication lists, and ICD-10 codes that tell you absolutely nothing about the patient or the physician’s thought process.

Recently, while reviewing malpractice cases, I saw some where I thought that the EHR was contributing to the problem. Medication lists that showed everything a patient had ever taken, without showing when some were discontinued. Prescribing lists that allowed you to enter only certain doses or schedules, therefore blocking the physician from tailoring them to a specific person’s needs. Physical exam forms that allowed only positive or negative answers, with nowhere to comment on unusual findings.

Of course, I’m just one person, so I thought “maybe it’s just me.” After all, a lot of practices out there use EHRs.

But apparently I’m not the only one. A recent report by one of the nation’s largest doctor-owned malpractice companies found that EHRs may increase the risks of liability and medical errors. In 2013, The Doctor’s Company found 28 closed claims where the EHR contributed, and 26 in just the first half of 2014.

These include both technological problems with the systems and human error in their use. Troubles included erroneous medication dose and schedules, diagnosis-related errors, and the sadly common pitfall of cutting and pasting previous notes without modification.

Medicine has always been, and will always be, a thinking profession, and trying to have computers take part of this job off of us is never good. EHRs, while they have advantages in convenience and space savings, are as imperfect as those who write them.

Patients are not one-size-fits-all, and individual treatments have to be customized in ways that current systems often don’t recognize, sometimes with sad consequences for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Buy our EHR. Come to a dinner and see our EHR. Our EHR is the best.

I hear that a lot, but am not rushing out to get one. Yes, I have an EHR, but it’s one I designed myself. It works very well for my dinky little practice, and I’m happy with it.

I get notes from practices that use commercial EHRs all the time. They’re usually a pile of gobbledygook, mixing labs, vital signs, medication lists, and ICD-10 codes that tell you absolutely nothing about the patient or the physician’s thought process.

Recently, while reviewing malpractice cases, I saw some where I thought that the EHR was contributing to the problem. Medication lists that showed everything a patient had ever taken, without showing when some were discontinued. Prescribing lists that allowed you to enter only certain doses or schedules, therefore blocking the physician from tailoring them to a specific person’s needs. Physical exam forms that allowed only positive or negative answers, with nowhere to comment on unusual findings.

Of course, I’m just one person, so I thought “maybe it’s just me.” After all, a lot of practices out there use EHRs.

But apparently I’m not the only one. A recent report by one of the nation’s largest doctor-owned malpractice companies found that EHRs may increase the risks of liability and medical errors. In 2013, The Doctor’s Company found 28 closed claims where the EHR contributed, and 26 in just the first half of 2014.

These include both technological problems with the systems and human error in their use. Troubles included erroneous medication dose and schedules, diagnosis-related errors, and the sadly common pitfall of cutting and pasting previous notes without modification.

Medicine has always been, and will always be, a thinking profession, and trying to have computers take part of this job off of us is never good. EHRs, while they have advantages in convenience and space savings, are as imperfect as those who write them.

Patients are not one-size-fits-all, and individual treatments have to be customized in ways that current systems often don’t recognize, sometimes with sad consequences for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Buy our EHR. Come to a dinner and see our EHR. Our EHR is the best.

I hear that a lot, but am not rushing out to get one. Yes, I have an EHR, but it’s one I designed myself. It works very well for my dinky little practice, and I’m happy with it.

I get notes from practices that use commercial EHRs all the time. They’re usually a pile of gobbledygook, mixing labs, vital signs, medication lists, and ICD-10 codes that tell you absolutely nothing about the patient or the physician’s thought process.

Recently, while reviewing malpractice cases, I saw some where I thought that the EHR was contributing to the problem. Medication lists that showed everything a patient had ever taken, without showing when some were discontinued. Prescribing lists that allowed you to enter only certain doses or schedules, therefore blocking the physician from tailoring them to a specific person’s needs. Physical exam forms that allowed only positive or negative answers, with nowhere to comment on unusual findings.

Of course, I’m just one person, so I thought “maybe it’s just me.” After all, a lot of practices out there use EHRs.

But apparently I’m not the only one. A recent report by one of the nation’s largest doctor-owned malpractice companies found that EHRs may increase the risks of liability and medical errors. In 2013, The Doctor’s Company found 28 closed claims where the EHR contributed, and 26 in just the first half of 2014.

These include both technological problems with the systems and human error in their use. Troubles included erroneous medication dose and schedules, diagnosis-related errors, and the sadly common pitfall of cutting and pasting previous notes without modification.

Medicine has always been, and will always be, a thinking profession, and trying to have computers take part of this job off of us is never good. EHRs, while they have advantages in convenience and space savings, are as imperfect as those who write them.

Patients are not one-size-fits-all, and individual treatments have to be customized in ways that current systems often don’t recognize, sometimes with sad consequences for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

PARIS – Transcatheter mitral valve replacement using a repurposed transcatheter aortic valve in patients with severe symptomatic native mitral valve disease and severe mitral annular calcification is feasible and may be an option in carefully selected patients who aren’t candidates for surgery, Mayra Guerrero, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

However, at this early point in development, the procedure is associated with an exceptionally steep learning curve, said Dr. Guerrero, director of cardiac structural interventions at the NorthShore University Health System in Evanston, Ill.

She presented the procedural and 30-day outcomes for the first 104 patients entered into a global registry encompassing 47 centers in 11 countries. Nearly 90% of patients received an Edwards SAPIEN XT or SAPIEN 3 valve. The EuroPCR results update an earlier report on the first 64 patients in the registry (JACC Cardiovasc Interv. 2016 Jul 11;9[13]:1361-71).

The results, she said, are reminiscent of the early days in transcatheter aortic valve replacement, which were marked by an initial very high early mortality rate that fell dramatically as technology and techniques improved.

“We know that there are important things we need to improve. Left ventricular outflow tract obstruction is the Achilles heel of this procedure; we need to work on its prevention and management. We need better annulus sizing methods. We need to find the best delivery method and improve our patient selection in order to avoid taking on patients who are too sick. Still, even during this early experience, the technical success rate has improved, and 30-day mortality continues to drop,” Dr. Guerrero said.

Indeed, the 30-day all-cause mortality rate of 25% in the first 104 patients doesn’t tell the whole story. The rate was 37.5% in the first third of patients, fell to 21.9% in the second tertile, and then to 15% in the most recent tertile.

Similarly, the technical success rate of the procedure according to Mitral Valve Academic Research Consortium criteria improved from 62.5% in the first tertile of patients to 84.4% and 80% in the second and third, respectively, she continued.

The rates of almost all complications went down with greater operator experience, too. The notable exception was left ventricular outflow tract obstruction (LVOTO). It occurred in 12.5% of patients in the first tertile and remained unchanged in the third.

It’s noteworthy that the majority of deaths were noncardiac in nature. Patients with mitral annular calcification are a high-risk group even before they develop valvular dysfunction. They are typically older and have multiple comorbidities. Participants in the global registry had a mean Society of Thoracic Surgeons score of 14.4; 38% had diabetes, 45% had chronic obstructive pulmonary disease, 35% had heart failure, 34% had previously undergone coronary artery bypass surgery, and roughly half of patients had a prior aortic valve replacement.

Causes of noncardiac mortality within 30 days included multiorgan failure in 8.6% of subjects, pneumonia in 2.9%, infection in 1.9%, and one fatal thoracentesis-related bleeding complication.

Cardiovascular deaths included two cases due to left ventricular perforation, two fatal strokes, an MI due to air emboli, a lethal complete atrioventricular block, and three deaths owing to LVOTO.

Alcohol ablation met with some success as a bailout treatment in cases of LVOTO with hemodynamic compromise after transmitral valve replacement in the global registry. All six treated patients had significant improvement initially, although the LVOTO recurred the next day in one instance. Four of the six patients were discharged from the hospital. One patient died because of atrioventricular block, and another from multiorgan failure 3 weeks after alcohol ablation of the LVOTO.

Dr. Guerrero has been a leader in this new field. She reported the first percutaneous implantation of a balloon expandable transcatheter valve in a native mitral valve without a surgical incision (Catheter Cardiovasc Interv. 2014 Jun 1;83[7]:E287-91), and more recently, together with coworkers developed a percutaneous alcohol ablation technique for acute reduction of LVOTO due to transcatheter mitral valve replacement (Catheter Cardiovasc Interv. 2016 Jul 5. doi:10.1002/ccd.26649).

She is now the principal investigator in the ongoing Mitral Implantation of Transcatheter Valves (MITRAL) trial, a physician-sponsored, 90-patient pilot study underway at six U.S. sites. MITRAL is recruiting three patient populations for transcatheter mitral valve replacement: patients like those in the global registry, with native mitral valve disease and severe mitral annular calcification; those with a symptomatic failing surgical ring with severe mitral regurgitation or stenosis; and patients with a symptomatic failing surgical bioprosthesis with severe mitral regurgitation or stenosis.

Discussant Nicolo Piazza, MD, of McGill University, Montreal, said transcatheter mitral valve replacement in mitral valve disease with severe mitral annular calcification in patients unsuitable for surgery “definitely represents an unmet clinical need in our practice today.” But he urged caution in interpreting the global registry data.

“This is a real world registry study with inherent selection bias and physician reporting bias,” the cardiologist said.

“We are leveraging a therapy from the aortic field into the mitral field. Of course, we do not have dedicated devices yet to treat these patients. The main finding of this study is that the procedure is actually feasible,” Dr. Piazza said.

Still, it’s sobering that at least 1 in 10 treated patients experiences LVOTO, 1 in 10 requires a second valve, and technical success is achieved in 3 out of 4 patients, he added.

Dr. Piazza predicted that multislice CT scans will be “extremely important” in refining patient selection criteria for the procedure, and echocardiography will be helpful in understanding the optimal procedural techniques and viewing angles. Work also needs to be done on developing optimal anticoagulation protocols in order to avoid valve thrombosis.

Dr. Guerrero reported serving as a consultant to Edwards Lifesciences. Dr. Piazza is a consultant to Medtronic and MicroPort.

bjancin@frontlinemedcom.com

PARIS – Transcatheter mitral valve replacement using a repurposed transcatheter aortic valve in patients with severe symptomatic native mitral valve disease and severe mitral annular calcification is feasible and may be an option in carefully selected patients who aren’t candidates for surgery, Mayra Guerrero, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

However, at this early point in development, the procedure is associated with an exceptionally steep learning curve, said Dr. Guerrero, director of cardiac structural interventions at the NorthShore University Health System in Evanston, Ill.

She presented the procedural and 30-day outcomes for the first 104 patients entered into a global registry encompassing 47 centers in 11 countries. Nearly 90% of patients received an Edwards SAPIEN XT or SAPIEN 3 valve. The EuroPCR results update an earlier report on the first 64 patients in the registry (JACC Cardiovasc Interv. 2016 Jul 11;9[13]:1361-71).

The results, she said, are reminiscent of the early days in transcatheter aortic valve replacement, which were marked by an initial very high early mortality rate that fell dramatically as technology and techniques improved.

“We know that there are important things we need to improve. Left ventricular outflow tract obstruction is the Achilles heel of this procedure; we need to work on its prevention and management. We need better annulus sizing methods. We need to find the best delivery method and improve our patient selection in order to avoid taking on patients who are too sick. Still, even during this early experience, the technical success rate has improved, and 30-day mortality continues to drop,” Dr. Guerrero said.

Indeed, the 30-day all-cause mortality rate of 25% in the first 104 patients doesn’t tell the whole story. The rate was 37.5% in the first third of patients, fell to 21.9% in the second tertile, and then to 15% in the most recent tertile.

Similarly, the technical success rate of the procedure according to Mitral Valve Academic Research Consortium criteria improved from 62.5% in the first tertile of patients to 84.4% and 80% in the second and third, respectively, she continued.

The rates of almost all complications went down with greater operator experience, too. The notable exception was left ventricular outflow tract obstruction (LVOTO). It occurred in 12.5% of patients in the first tertile and remained unchanged in the third.

It’s noteworthy that the majority of deaths were noncardiac in nature. Patients with mitral annular calcification are a high-risk group even before they develop valvular dysfunction. They are typically older and have multiple comorbidities. Participants in the global registry had a mean Society of Thoracic Surgeons score of 14.4; 38% had diabetes, 45% had chronic obstructive pulmonary disease, 35% had heart failure, 34% had previously undergone coronary artery bypass surgery, and roughly half of patients had a prior aortic valve replacement.

Causes of noncardiac mortality within 30 days included multiorgan failure in 8.6% of subjects, pneumonia in 2.9%, infection in 1.9%, and one fatal thoracentesis-related bleeding complication.

Cardiovascular deaths included two cases due to left ventricular perforation, two fatal strokes, an MI due to air emboli, a lethal complete atrioventricular block, and three deaths owing to LVOTO.

Alcohol ablation met with some success as a bailout treatment in cases of LVOTO with hemodynamic compromise after transmitral valve replacement in the global registry. All six treated patients had significant improvement initially, although the LVOTO recurred the next day in one instance. Four of the six patients were discharged from the hospital. One patient died because of atrioventricular block, and another from multiorgan failure 3 weeks after alcohol ablation of the LVOTO.

Dr. Guerrero has been a leader in this new field. She reported the first percutaneous implantation of a balloon expandable transcatheter valve in a native mitral valve without a surgical incision (Catheter Cardiovasc Interv. 2014 Jun 1;83[7]:E287-91), and more recently, together with coworkers developed a percutaneous alcohol ablation technique for acute reduction of LVOTO due to transcatheter mitral valve replacement (Catheter Cardiovasc Interv. 2016 Jul 5. doi:10.1002/ccd.26649).

She is now the principal investigator in the ongoing Mitral Implantation of Transcatheter Valves (MITRAL) trial, a physician-sponsored, 90-patient pilot study underway at six U.S. sites. MITRAL is recruiting three patient populations for transcatheter mitral valve replacement: patients like those in the global registry, with native mitral valve disease and severe mitral annular calcification; those with a symptomatic failing surgical ring with severe mitral regurgitation or stenosis; and patients with a symptomatic failing surgical bioprosthesis with severe mitral regurgitation or stenosis.

Discussant Nicolo Piazza, MD, of McGill University, Montreal, said transcatheter mitral valve replacement in mitral valve disease with severe mitral annular calcification in patients unsuitable for surgery “definitely represents an unmet clinical need in our practice today.” But he urged caution in interpreting the global registry data.

“This is a real world registry study with inherent selection bias and physician reporting bias,” the cardiologist said.

“We are leveraging a therapy from the aortic field into the mitral field. Of course, we do not have dedicated devices yet to treat these patients. The main finding of this study is that the procedure is actually feasible,” Dr. Piazza said.

Still, it’s sobering that at least 1 in 10 treated patients experiences LVOTO, 1 in 10 requires a second valve, and technical success is achieved in 3 out of 4 patients, he added.

Dr. Piazza predicted that multislice CT scans will be “extremely important” in refining patient selection criteria for the procedure, and echocardiography will be helpful in understanding the optimal procedural techniques and viewing angles. Work also needs to be done on developing optimal anticoagulation protocols in order to avoid valve thrombosis.

Dr. Guerrero reported serving as a consultant to Edwards Lifesciences. Dr. Piazza is a consultant to Medtronic and MicroPort.

bjancin@frontlinemedcom.com

PARIS – Transcatheter mitral valve replacement using a repurposed transcatheter aortic valve in patients with severe symptomatic native mitral valve disease and severe mitral annular calcification is feasible and may be an option in carefully selected patients who aren’t candidates for surgery, Mayra Guerrero, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

However, at this early point in development, the procedure is associated with an exceptionally steep learning curve, said Dr. Guerrero, director of cardiac structural interventions at the NorthShore University Health System in Evanston, Ill.

She presented the procedural and 30-day outcomes for the first 104 patients entered into a global registry encompassing 47 centers in 11 countries. Nearly 90% of patients received an Edwards SAPIEN XT or SAPIEN 3 valve. The EuroPCR results update an earlier report on the first 64 patients in the registry (JACC Cardiovasc Interv. 2016 Jul 11;9[13]:1361-71).

The results, she said, are reminiscent of the early days in transcatheter aortic valve replacement, which were marked by an initial very high early mortality rate that fell dramatically as technology and techniques improved.

“We know that there are important things we need to improve. Left ventricular outflow tract obstruction is the Achilles heel of this procedure; we need to work on its prevention and management. We need better annulus sizing methods. We need to find the best delivery method and improve our patient selection in order to avoid taking on patients who are too sick. Still, even during this early experience, the technical success rate has improved, and 30-day mortality continues to drop,” Dr. Guerrero said.

Indeed, the 30-day all-cause mortality rate of 25% in the first 104 patients doesn’t tell the whole story. The rate was 37.5% in the first third of patients, fell to 21.9% in the second tertile, and then to 15% in the most recent tertile.

Similarly, the technical success rate of the procedure according to Mitral Valve Academic Research Consortium criteria improved from 62.5% in the first tertile of patients to 84.4% and 80% in the second and third, respectively, she continued.

The rates of almost all complications went down with greater operator experience, too. The notable exception was left ventricular outflow tract obstruction (LVOTO). It occurred in 12.5% of patients in the first tertile and remained unchanged in the third.

It’s noteworthy that the majority of deaths were noncardiac in nature. Patients with mitral annular calcification are a high-risk group even before they develop valvular dysfunction. They are typically older and have multiple comorbidities. Participants in the global registry had a mean Society of Thoracic Surgeons score of 14.4; 38% had diabetes, 45% had chronic obstructive pulmonary disease, 35% had heart failure, 34% had previously undergone coronary artery bypass surgery, and roughly half of patients had a prior aortic valve replacement.

Causes of noncardiac mortality within 30 days included multiorgan failure in 8.6% of subjects, pneumonia in 2.9%, infection in 1.9%, and one fatal thoracentesis-related bleeding complication.

Cardiovascular deaths included two cases due to left ventricular perforation, two fatal strokes, an MI due to air emboli, a lethal complete atrioventricular block, and three deaths owing to LVOTO.

Alcohol ablation met with some success as a bailout treatment in cases of LVOTO with hemodynamic compromise after transmitral valve replacement in the global registry. All six treated patients had significant improvement initially, although the LVOTO recurred the next day in one instance. Four of the six patients were discharged from the hospital. One patient died because of atrioventricular block, and another from multiorgan failure 3 weeks after alcohol ablation of the LVOTO.

Dr. Guerrero has been a leader in this new field. She reported the first percutaneous implantation of a balloon expandable transcatheter valve in a native mitral valve without a surgical incision (Catheter Cardiovasc Interv. 2014 Jun 1;83[7]:E287-91), and more recently, together with coworkers developed a percutaneous alcohol ablation technique for acute reduction of LVOTO due to transcatheter mitral valve replacement (Catheter Cardiovasc Interv. 2016 Jul 5. doi:10.1002/ccd.26649).

She is now the principal investigator in the ongoing Mitral Implantation of Transcatheter Valves (MITRAL) trial, a physician-sponsored, 90-patient pilot study underway at six U.S. sites. MITRAL is recruiting three patient populations for transcatheter mitral valve replacement: patients like those in the global registry, with native mitral valve disease and severe mitral annular calcification; those with a symptomatic failing surgical ring with severe mitral regurgitation or stenosis; and patients with a symptomatic failing surgical bioprosthesis with severe mitral regurgitation or stenosis.

Discussant Nicolo Piazza, MD, of McGill University, Montreal, said transcatheter mitral valve replacement in mitral valve disease with severe mitral annular calcification in patients unsuitable for surgery “definitely represents an unmet clinical need in our practice today.” But he urged caution in interpreting the global registry data.

“This is a real world registry study with inherent selection bias and physician reporting bias,” the cardiologist said.

“We are leveraging a therapy from the aortic field into the mitral field. Of course, we do not have dedicated devices yet to treat these patients. The main finding of this study is that the procedure is actually feasible,” Dr. Piazza said.

Still, it’s sobering that at least 1 in 10 treated patients experiences LVOTO, 1 in 10 requires a second valve, and technical success is achieved in 3 out of 4 patients, he added.

Dr. Piazza predicted that multislice CT scans will be “extremely important” in refining patient selection criteria for the procedure, and echocardiography will be helpful in understanding the optimal procedural techniques and viewing angles. Work also needs to be done on developing optimal anticoagulation protocols in order to avoid valve thrombosis.

Dr. Guerrero reported serving as a consultant to Edwards Lifesciences. Dr. Piazza is a consultant to Medtronic and MicroPort.

bjancin@frontlinemedcom.com