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Results prove lasting from iCBT in mild to moderate depression
SAN DIEGO – Cognitive-behavioral therapy (CPT) interventions delivered online are effective in reducing symptoms of mild to moderate depression in adults, according to results presented at the annual meeting of the American Psychiatric Association.
The findings, presented by Charles Koransky, MD, of the University of Maryland, Baltimore, derive from a meta-analysis of 14 randomized studies, conducted between 2005 and 2015, that enrolled more than 1,600 patients aged 18 years and older in Europe and Australia.
Patients in the studies were not receiving any other form of therapy, though some studies allowed concurrent use of antidepressant medications.
Results from patients assigned to the web-based interventions, which lasted 1 month or more, were compared with those who remained on waiting lists for treatment. Most of the interventions included brief clinician contact as part of their designs. Others were entirely self-guided.
Dr. Koransky and his colleagues found that completion rates were high, with between 55% and 93% of patients finishing the assigned interventions. The intervention groups saw significant improvement in symptoms after the online CBT interventions, with a standard mean difference of 0.74 (95% confidence interval, 0.63-0.86; P less than 0.001), compared with patients randomized to wait lists.
For the 11 studies that included between 3- and 6-months’ follow-up, improvement in depressive symptoms was seen to be durable, with a large SMD of 0.85 (95% CI, 0.79-0.90; P less than 0.001). “This shows that the effects last,” Dr. Koransky told conference attendees.
Dr. Koransky noted that statistically significant difference was seen between the studies with interventions that included clinician contact and those that did not. “This is probably because the clinician contact in the studies was brief, 10-minute chats or emails,” he said.
“Internet-based CBT leads to immediate and sustained reduction of depressive symptoms, which is consistent with analyses in the past,” Dr. Koransky said. “We also found that iCBT may be a good option for patients not able to access traditional face-to-face therapy,” he said, noting that several of the interventions in the study were designed to help address access issues in rural Australia.
Dr. Koransky noted that the results might not be generalizable because of the large portion of female patients across studies – more than 75% – and the fact that all patients were recruited through advertisements, suggesting that these were “highly motivated participants seeking some alleviation of their symptoms.” Another limitation of the study was a lack of uniformity across iCBT interfaces.
Nonetheless, he said, the findings have implications for U.S. practitioners, particularly primary care doctors in regions with poor access to mental health specialists.
Internet-delivered CBT may be “great for people in rural settings, especially if prescribed by primary care providers who don’t have the training to provide CBT,” he said.
Dr. Koransky said his group aimed to study these interventions in a U.S. population and among patients referred to iCBT by their primary care doctors. The researchers disclosed no conflicts of interest related to their findings.
SAN DIEGO – Cognitive-behavioral therapy (CPT) interventions delivered online are effective in reducing symptoms of mild to moderate depression in adults, according to results presented at the annual meeting of the American Psychiatric Association.
The findings, presented by Charles Koransky, MD, of the University of Maryland, Baltimore, derive from a meta-analysis of 14 randomized studies, conducted between 2005 and 2015, that enrolled more than 1,600 patients aged 18 years and older in Europe and Australia.
Patients in the studies were not receiving any other form of therapy, though some studies allowed concurrent use of antidepressant medications.
Results from patients assigned to the web-based interventions, which lasted 1 month or more, were compared with those who remained on waiting lists for treatment. Most of the interventions included brief clinician contact as part of their designs. Others were entirely self-guided.
Dr. Koransky and his colleagues found that completion rates were high, with between 55% and 93% of patients finishing the assigned interventions. The intervention groups saw significant improvement in symptoms after the online CBT interventions, with a standard mean difference of 0.74 (95% confidence interval, 0.63-0.86; P less than 0.001), compared with patients randomized to wait lists.
For the 11 studies that included between 3- and 6-months’ follow-up, improvement in depressive symptoms was seen to be durable, with a large SMD of 0.85 (95% CI, 0.79-0.90; P less than 0.001). “This shows that the effects last,” Dr. Koransky told conference attendees.
Dr. Koransky noted that statistically significant difference was seen between the studies with interventions that included clinician contact and those that did not. “This is probably because the clinician contact in the studies was brief, 10-minute chats or emails,” he said.
“Internet-based CBT leads to immediate and sustained reduction of depressive symptoms, which is consistent with analyses in the past,” Dr. Koransky said. “We also found that iCBT may be a good option for patients not able to access traditional face-to-face therapy,” he said, noting that several of the interventions in the study were designed to help address access issues in rural Australia.
Dr. Koransky noted that the results might not be generalizable because of the large portion of female patients across studies – more than 75% – and the fact that all patients were recruited through advertisements, suggesting that these were “highly motivated participants seeking some alleviation of their symptoms.” Another limitation of the study was a lack of uniformity across iCBT interfaces.
Nonetheless, he said, the findings have implications for U.S. practitioners, particularly primary care doctors in regions with poor access to mental health specialists.
Internet-delivered CBT may be “great for people in rural settings, especially if prescribed by primary care providers who don’t have the training to provide CBT,” he said.
Dr. Koransky said his group aimed to study these interventions in a U.S. population and among patients referred to iCBT by their primary care doctors. The researchers disclosed no conflicts of interest related to their findings.
SAN DIEGO – Cognitive-behavioral therapy (CPT) interventions delivered online are effective in reducing symptoms of mild to moderate depression in adults, according to results presented at the annual meeting of the American Psychiatric Association.
The findings, presented by Charles Koransky, MD, of the University of Maryland, Baltimore, derive from a meta-analysis of 14 randomized studies, conducted between 2005 and 2015, that enrolled more than 1,600 patients aged 18 years and older in Europe and Australia.
Patients in the studies were not receiving any other form of therapy, though some studies allowed concurrent use of antidepressant medications.
Results from patients assigned to the web-based interventions, which lasted 1 month or more, were compared with those who remained on waiting lists for treatment. Most of the interventions included brief clinician contact as part of their designs. Others were entirely self-guided.
Dr. Koransky and his colleagues found that completion rates were high, with between 55% and 93% of patients finishing the assigned interventions. The intervention groups saw significant improvement in symptoms after the online CBT interventions, with a standard mean difference of 0.74 (95% confidence interval, 0.63-0.86; P less than 0.001), compared with patients randomized to wait lists.
For the 11 studies that included between 3- and 6-months’ follow-up, improvement in depressive symptoms was seen to be durable, with a large SMD of 0.85 (95% CI, 0.79-0.90; P less than 0.001). “This shows that the effects last,” Dr. Koransky told conference attendees.
Dr. Koransky noted that statistically significant difference was seen between the studies with interventions that included clinician contact and those that did not. “This is probably because the clinician contact in the studies was brief, 10-minute chats or emails,” he said.
“Internet-based CBT leads to immediate and sustained reduction of depressive symptoms, which is consistent with analyses in the past,” Dr. Koransky said. “We also found that iCBT may be a good option for patients not able to access traditional face-to-face therapy,” he said, noting that several of the interventions in the study were designed to help address access issues in rural Australia.
Dr. Koransky noted that the results might not be generalizable because of the large portion of female patients across studies – more than 75% – and the fact that all patients were recruited through advertisements, suggesting that these were “highly motivated participants seeking some alleviation of their symptoms.” Another limitation of the study was a lack of uniformity across iCBT interfaces.
Nonetheless, he said, the findings have implications for U.S. practitioners, particularly primary care doctors in regions with poor access to mental health specialists.
Internet-delivered CBT may be “great for people in rural settings, especially if prescribed by primary care providers who don’t have the training to provide CBT,” he said.
Dr. Koransky said his group aimed to study these interventions in a U.S. population and among patients referred to iCBT by their primary care doctors. The researchers disclosed no conflicts of interest related to their findings.
AT APA
Key clinical point: CBT delivered online with minimal therapist involvement can produce immediate and sustained reduction of depressive symptoms.
Major finding: Treatment groups saw a standard mean difference of 0.74 vs. nontreated patients immediately after intervention and 0.85 after 3-6 months follow-up (P less than 0.001 for both) .
Data source: A meta-analysis of 14 randomized, controlled trials from Europe and Australia randomizing 1,600 patients to online CBT or a wait list for care.
Disclosures: The researchers disclosed no conflicts of interest related to their findings.
Compounding rules challenge practice norms
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
Eliminating hepatitis in the United States: A road map
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
FROM THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE
Common gut yeast may exacerbate IBD
A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.
While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.
In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).
Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.
To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”
Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.
While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.
In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).
Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.
To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”
Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.
While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.
In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).
Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.
To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”
Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point:
Major finding: Sterile mice inoculated with S. cerevisiae and treated to induce colitis had more tissue damage than untreated mice or those treated with another type of yeast.
Data source: An experimental study on mice inoculated with one of two yeasts, then treated to induce colitislike symptoms.
Disclosures: Study authors had multiple sources of individual grant funding but no commercial conflicts of interest.
AKI seen in 64% of children hospitalized with diabetic ketoacidosis
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
FROM JAMA PEDIATRICS
Key clinical point: Acute kidney injury may occur in up to two-thirds of children hospitalized for diabetic ketoacidosis.
Major finding: In a cohort of 165 children hospitalized with DKA, 64% developed AKI. Of these, 45% had stage 2 AKI and 20% had stage 3.
Data source: A retrospective single-site cohort study of records from 165 children with DKA hospitalized from 2008 to 2013.
Disclosures: The researchers disclosed no outside funding or relevant financial conflicts of interest.
Early elective deliveries occur in less than 2% of births
Early elective delivery in the United States is at an all-time low of 1.9%, down from 17% in 2010, according to a report by a nonprofit group that monitors safety and care quality in hospitals.
Early elective delivery comprises Cesarean deliveries or inductions performed before 39 weeks without medical necessity, and higher rates are considered a barometer of poor labor management in hospitals. For its annual report on maternity practices, published Feb. 28, the Leapfrog Group, a Washington, D.C.–based nonprofit, collected voluntarily reported data from 1,859 hospitals, or about half of the nation’s hospitals, in 2016.
The rate of Cesarean deliveries among first-time mothers at 37 or more weeks of gestation with babies in the head-down position (NTSV C-section) was 25.8% of deliveries in 2016, with little change from the previous year. Leapfrog’s target rate for NTSV C-section is 23.9% or lower. The group reported considerable geographic variation in C-section rates, with 32.1% for Louisiana, the highest seen in the survey, and 17.1% for New Mexico, the lowest.
The group did not note significant differences across hospital type, finding that urban, rural, teaching and nonteaching hospitals saw similar likelihoods of meeting the organization’s target standards for early elective delivery, episiotomy, and NTSV C-section.
“This year’s Leapfrog data underscores that many of the conventional assumptions for how to pick a ‘good hospital’ do not bear out – rates among teaching hospitals that may care for ‘sicker’ patients are similar to those at nonteaching hospitals. Rates at urban hospitals are similar to those at rural hospitals,” Neel Shah, MD, of Harvard Medical School, Boston, wrote in the report.
Early elective delivery in the United States is at an all-time low of 1.9%, down from 17% in 2010, according to a report by a nonprofit group that monitors safety and care quality in hospitals.
Early elective delivery comprises Cesarean deliveries or inductions performed before 39 weeks without medical necessity, and higher rates are considered a barometer of poor labor management in hospitals. For its annual report on maternity practices, published Feb. 28, the Leapfrog Group, a Washington, D.C.–based nonprofit, collected voluntarily reported data from 1,859 hospitals, or about half of the nation’s hospitals, in 2016.
The rate of Cesarean deliveries among first-time mothers at 37 or more weeks of gestation with babies in the head-down position (NTSV C-section) was 25.8% of deliveries in 2016, with little change from the previous year. Leapfrog’s target rate for NTSV C-section is 23.9% or lower. The group reported considerable geographic variation in C-section rates, with 32.1% for Louisiana, the highest seen in the survey, and 17.1% for New Mexico, the lowest.
The group did not note significant differences across hospital type, finding that urban, rural, teaching and nonteaching hospitals saw similar likelihoods of meeting the organization’s target standards for early elective delivery, episiotomy, and NTSV C-section.
“This year’s Leapfrog data underscores that many of the conventional assumptions for how to pick a ‘good hospital’ do not bear out – rates among teaching hospitals that may care for ‘sicker’ patients are similar to those at nonteaching hospitals. Rates at urban hospitals are similar to those at rural hospitals,” Neel Shah, MD, of Harvard Medical School, Boston, wrote in the report.
Early elective delivery in the United States is at an all-time low of 1.9%, down from 17% in 2010, according to a report by a nonprofit group that monitors safety and care quality in hospitals.
Early elective delivery comprises Cesarean deliveries or inductions performed before 39 weeks without medical necessity, and higher rates are considered a barometer of poor labor management in hospitals. For its annual report on maternity practices, published Feb. 28, the Leapfrog Group, a Washington, D.C.–based nonprofit, collected voluntarily reported data from 1,859 hospitals, or about half of the nation’s hospitals, in 2016.
The rate of Cesarean deliveries among first-time mothers at 37 or more weeks of gestation with babies in the head-down position (NTSV C-section) was 25.8% of deliveries in 2016, with little change from the previous year. Leapfrog’s target rate for NTSV C-section is 23.9% or lower. The group reported considerable geographic variation in C-section rates, with 32.1% for Louisiana, the highest seen in the survey, and 17.1% for New Mexico, the lowest.
The group did not note significant differences across hospital type, finding that urban, rural, teaching and nonteaching hospitals saw similar likelihoods of meeting the organization’s target standards for early elective delivery, episiotomy, and NTSV C-section.
“This year’s Leapfrog data underscores that many of the conventional assumptions for how to pick a ‘good hospital’ do not bear out – rates among teaching hospitals that may care for ‘sicker’ patients are similar to those at nonteaching hospitals. Rates at urban hospitals are similar to those at rural hospitals,” Neel Shah, MD, of Harvard Medical School, Boston, wrote in the report.
Cancers in patients deemed lowest risk under Lung-RADS
A reporting system for lung cancer screening with low-dose computed tomography may underemphasize important abnormal findings other than nodules, researchers say, potentially leading to missed malignancies.
The American College of Radiology Lung Imaging Reporting and Data System, or Lung-RADS, was introduced in 2014 to standardize reporting for low-dose CT findings and also to reduce false-positive rates, by applying tighter criteria that was used in the National Lung Screening Trial.
Lung-RADS does not have specific reporting categories for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules, even though these can indicate malignancy. It does allow for the inclusion of what is called an “S” code to indicate clinically significant findings other than nodules.
In the March 2017 issue of CHEST, Hiren Mehta, MD, and his colleagues at the University of Florida in Gainesville, report on four cases from their center in which patients with these pathologies had their scans read as Lung-RADS category 1, indicating a less than 1% likelihood of malignancy. No S codes were added to their reports. Subsequent testing in these patients revealed cancers (CHEST. 2017 March;151[3]:525-26).
The four cases were:
- A 56-year-old male with hilar and mediastinal adenopathy who was recommended for repeat screening at 12 months. The patient presented 6 months later with pneumonia; biopsy revealed large cell lung cancer.
- A 76-year-old male with paratracheal lymph nodes and a solitary subcarinal lymph node. A subsequent biopsy revealed adenocarcinoma.
- A 67-year-old male whose scan showed bulky hilar and mediastinal adenopathy. Subsequent testing revealed Hodgkin’s lymphoma.
- A 75-year-old female whose scan showed a small pleural effusion and no nodules. Repeat scanning at 1 year showed enlargement of the effusion and lung adenocarcinoma.
Dr. Mehta and colleagues noted in their analysis that Lung-RADS has not been studied prospectively in real practice settings and that the four cases – two of which involved delayed diagnosis – reveal “a significant limitation” of Lung-RADS.
“Based on our experience, we believe that particular caution should be exercised in reporting Lung-RADS 1 category for patients with adenopathy/pleural effusion with no lung nodules, as a majority of the lung cancer screening scans will be ordered by [primary care providers] ... [As] with any new system, an ongoing evaluation of the performance of Lung-RADS should be conducted so that the sensitivity and mortality benefit seen in the [National Lung Screening Trial] is not compromised.”
We strongly believe, based on our experience with these 4 cases that the new version of Lung-RADS 2.0 should [account for shortcomings of the current Lung-RADS] and have a separate category for findings that are highly suspicious for malignancy but do not have an accompanying lung nodule,” they wrote.
The investigators did not disclose outside funding or conflicts of interest related to their findings.
*This story was updated March 16, 2017, with the correct journal source.
The performance of lung cancer screening does not absolve the interpreter from pointing out clinically important findings whether or not they are related to lung cancer. Review of the entire examination for other potentially significant findings should be performed and reported in accordance with applicable standards, says The Joint American College of Radiology and Society of Thoracic Radiology practice parameter for the performance and reporting of lung cancer screening thoracic CT. In addition to adenopathy and pleural effusion, detection of abnormalities such as severe coronary artery calcifications, aortic aneurysms, severe emphysema and suspicious masses in the upper abdomen should be called out not just in the body of the report, but also in the final impression so that it is easily available to the reader of the report.
Lung-RADS recognizes the importance of incidental findings with an additional coding letter, the “S” code. The letter “S” should be attached any time there is an abnormality considered clinically important that is not a pulmonary nodule. For the cases presented in this study, the appropriate code for the subjects should have been Lung-RADS 1S with a specific recommendation for the management of the “S” findings. It is incumbent on individuals interpreting these examinations to appropriately account for and report all significant findings, not simply lung nodules, and to be familiar with and understand Lung-RADS. Judicious use of the Lung-RADS “S” code along with specific discussion of the report’s final impression is recommended as a means of improving communication.
James Ravenel, MD; Nichole Tanner, MD, MSCR, FCCP; and Gerard Silvestri, MD, MS, FCCP, are with the Medical University of South Carolina, Charleston. Dr. Tanner also is with the Ralph H. Johnson Veterans Affairs Hospital, Charleston.
These comments have been modified from an editorial accompanying Dr. Mehta and his colleagues’ study in CHEST (Chest. 2017 March;151[3]:539-43). The authors disclosed no conflicts of interest related to their editorial.
The performance of lung cancer screening does not absolve the interpreter from pointing out clinically important findings whether or not they are related to lung cancer. Review of the entire examination for other potentially significant findings should be performed and reported in accordance with applicable standards, says The Joint American College of Radiology and Society of Thoracic Radiology practice parameter for the performance and reporting of lung cancer screening thoracic CT. In addition to adenopathy and pleural effusion, detection of abnormalities such as severe coronary artery calcifications, aortic aneurysms, severe emphysema and suspicious masses in the upper abdomen should be called out not just in the body of the report, but also in the final impression so that it is easily available to the reader of the report.
Lung-RADS recognizes the importance of incidental findings with an additional coding letter, the “S” code. The letter “S” should be attached any time there is an abnormality considered clinically important that is not a pulmonary nodule. For the cases presented in this study, the appropriate code for the subjects should have been Lung-RADS 1S with a specific recommendation for the management of the “S” findings. It is incumbent on individuals interpreting these examinations to appropriately account for and report all significant findings, not simply lung nodules, and to be familiar with and understand Lung-RADS. Judicious use of the Lung-RADS “S” code along with specific discussion of the report’s final impression is recommended as a means of improving communication.
James Ravenel, MD; Nichole Tanner, MD, MSCR, FCCP; and Gerard Silvestri, MD, MS, FCCP, are with the Medical University of South Carolina, Charleston. Dr. Tanner also is with the Ralph H. Johnson Veterans Affairs Hospital, Charleston.
These comments have been modified from an editorial accompanying Dr. Mehta and his colleagues’ study in CHEST (Chest. 2017 March;151[3]:539-43). The authors disclosed no conflicts of interest related to their editorial.
The performance of lung cancer screening does not absolve the interpreter from pointing out clinically important findings whether or not they are related to lung cancer. Review of the entire examination for other potentially significant findings should be performed and reported in accordance with applicable standards, says The Joint American College of Radiology and Society of Thoracic Radiology practice parameter for the performance and reporting of lung cancer screening thoracic CT. In addition to adenopathy and pleural effusion, detection of abnormalities such as severe coronary artery calcifications, aortic aneurysms, severe emphysema and suspicious masses in the upper abdomen should be called out not just in the body of the report, but also in the final impression so that it is easily available to the reader of the report.
Lung-RADS recognizes the importance of incidental findings with an additional coding letter, the “S” code. The letter “S” should be attached any time there is an abnormality considered clinically important that is not a pulmonary nodule. For the cases presented in this study, the appropriate code for the subjects should have been Lung-RADS 1S with a specific recommendation for the management of the “S” findings. It is incumbent on individuals interpreting these examinations to appropriately account for and report all significant findings, not simply lung nodules, and to be familiar with and understand Lung-RADS. Judicious use of the Lung-RADS “S” code along with specific discussion of the report’s final impression is recommended as a means of improving communication.
James Ravenel, MD; Nichole Tanner, MD, MSCR, FCCP; and Gerard Silvestri, MD, MS, FCCP, are with the Medical University of South Carolina, Charleston. Dr. Tanner also is with the Ralph H. Johnson Veterans Affairs Hospital, Charleston.
These comments have been modified from an editorial accompanying Dr. Mehta and his colleagues’ study in CHEST (Chest. 2017 March;151[3]:539-43). The authors disclosed no conflicts of interest related to their editorial.
A reporting system for lung cancer screening with low-dose computed tomography may underemphasize important abnormal findings other than nodules, researchers say, potentially leading to missed malignancies.
The American College of Radiology Lung Imaging Reporting and Data System, or Lung-RADS, was introduced in 2014 to standardize reporting for low-dose CT findings and also to reduce false-positive rates, by applying tighter criteria that was used in the National Lung Screening Trial.
Lung-RADS does not have specific reporting categories for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules, even though these can indicate malignancy. It does allow for the inclusion of what is called an “S” code to indicate clinically significant findings other than nodules.
In the March 2017 issue of CHEST, Hiren Mehta, MD, and his colleagues at the University of Florida in Gainesville, report on four cases from their center in which patients with these pathologies had their scans read as Lung-RADS category 1, indicating a less than 1% likelihood of malignancy. No S codes were added to their reports. Subsequent testing in these patients revealed cancers (CHEST. 2017 March;151[3]:525-26).
The four cases were:
- A 56-year-old male with hilar and mediastinal adenopathy who was recommended for repeat screening at 12 months. The patient presented 6 months later with pneumonia; biopsy revealed large cell lung cancer.
- A 76-year-old male with paratracheal lymph nodes and a solitary subcarinal lymph node. A subsequent biopsy revealed adenocarcinoma.
- A 67-year-old male whose scan showed bulky hilar and mediastinal adenopathy. Subsequent testing revealed Hodgkin’s lymphoma.
- A 75-year-old female whose scan showed a small pleural effusion and no nodules. Repeat scanning at 1 year showed enlargement of the effusion and lung adenocarcinoma.
Dr. Mehta and colleagues noted in their analysis that Lung-RADS has not been studied prospectively in real practice settings and that the four cases – two of which involved delayed diagnosis – reveal “a significant limitation” of Lung-RADS.
“Based on our experience, we believe that particular caution should be exercised in reporting Lung-RADS 1 category for patients with adenopathy/pleural effusion with no lung nodules, as a majority of the lung cancer screening scans will be ordered by [primary care providers] ... [As] with any new system, an ongoing evaluation of the performance of Lung-RADS should be conducted so that the sensitivity and mortality benefit seen in the [National Lung Screening Trial] is not compromised.”
We strongly believe, based on our experience with these 4 cases that the new version of Lung-RADS 2.0 should [account for shortcomings of the current Lung-RADS] and have a separate category for findings that are highly suspicious for malignancy but do not have an accompanying lung nodule,” they wrote.
The investigators did not disclose outside funding or conflicts of interest related to their findings.
*This story was updated March 16, 2017, with the correct journal source.
A reporting system for lung cancer screening with low-dose computed tomography may underemphasize important abnormal findings other than nodules, researchers say, potentially leading to missed malignancies.
The American College of Radiology Lung Imaging Reporting and Data System, or Lung-RADS, was introduced in 2014 to standardize reporting for low-dose CT findings and also to reduce false-positive rates, by applying tighter criteria that was used in the National Lung Screening Trial.
Lung-RADS does not have specific reporting categories for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules, even though these can indicate malignancy. It does allow for the inclusion of what is called an “S” code to indicate clinically significant findings other than nodules.
In the March 2017 issue of CHEST, Hiren Mehta, MD, and his colleagues at the University of Florida in Gainesville, report on four cases from their center in which patients with these pathologies had their scans read as Lung-RADS category 1, indicating a less than 1% likelihood of malignancy. No S codes were added to their reports. Subsequent testing in these patients revealed cancers (CHEST. 2017 March;151[3]:525-26).
The four cases were:
- A 56-year-old male with hilar and mediastinal adenopathy who was recommended for repeat screening at 12 months. The patient presented 6 months later with pneumonia; biopsy revealed large cell lung cancer.
- A 76-year-old male with paratracheal lymph nodes and a solitary subcarinal lymph node. A subsequent biopsy revealed adenocarcinoma.
- A 67-year-old male whose scan showed bulky hilar and mediastinal adenopathy. Subsequent testing revealed Hodgkin’s lymphoma.
- A 75-year-old female whose scan showed a small pleural effusion and no nodules. Repeat scanning at 1 year showed enlargement of the effusion and lung adenocarcinoma.
Dr. Mehta and colleagues noted in their analysis that Lung-RADS has not been studied prospectively in real practice settings and that the four cases – two of which involved delayed diagnosis – reveal “a significant limitation” of Lung-RADS.
“Based on our experience, we believe that particular caution should be exercised in reporting Lung-RADS 1 category for patients with adenopathy/pleural effusion with no lung nodules, as a majority of the lung cancer screening scans will be ordered by [primary care providers] ... [As] with any new system, an ongoing evaluation of the performance of Lung-RADS should be conducted so that the sensitivity and mortality benefit seen in the [National Lung Screening Trial] is not compromised.”
We strongly believe, based on our experience with these 4 cases that the new version of Lung-RADS 2.0 should [account for shortcomings of the current Lung-RADS] and have a separate category for findings that are highly suspicious for malignancy but do not have an accompanying lung nodule,” they wrote.
The investigators did not disclose outside funding or conflicts of interest related to their findings.
*This story was updated March 16, 2017, with the correct journal source.
FROM CHEST*
Key clinical point: The current Lung-RADS system for classing low-dose CT results may not adequately capture cancer risk in patients with adenopathy or pleural effusion
Major finding: Four patients with adenopathy or pleural effusion in the absence of nodules were found to have lung cancer despite first scans classed as negative
Data source: Case reports from a university based center using Lung-RADS 1.0 in its lung cancer screening program.
Disclosures: The investigators did not disclose outside funding or conflicts of interest related to their findings.
Pigmented skin lesions lightened during melanoma immunotherapy
Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.
Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.
The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).
Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.
Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”
Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).
Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”
A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.
Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.
Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.
The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).
Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.
Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”
Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).
Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”
A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.
Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.
Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.
The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).
Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.
Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”
Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).
Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”
A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.
Key clinical point:
Major finding: Pembrolizumab and other PD-1 inhibitors may affect benign pigmented lesions.
Data source: A single-center, single-patient case report.
Disclosures: A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.
FDA approves sublingual immunotherapy for dust mite allergies
Odactra (Merck, Sharp & Dohme) had been approved in adults aged 18-65 years, with allergic rhinitis with or without conjunctivitis. The tablets offer an alternative to subcutaneous injections, the FDA said in a statement issued March 1. 
The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.
The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.
Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.
Odactra (Merck, Sharp & Dohme) had been approved in adults aged 18-65 years, with allergic rhinitis with or without conjunctivitis. The tablets offer an alternative to subcutaneous injections, the FDA said in a statement issued March 1.
The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.
The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.
Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.
Odactra (Merck, Sharp & Dohme) had been approved in adults aged 18-65 years, with allergic rhinitis with or without conjunctivitis. The tablets offer an alternative to subcutaneous injections, the FDA said in a statement issued March 1.
The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.
The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.
Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.
Use of IHC stains on rise in melanoma diagnosis
While there is little consensus on the ideal role of immunohistochemical (IHC) stains in the diagnosis of melanoma, their use increased dramatically over a 15-year period, according to results from a study.
Randie H. Kim, MD, PhD, and Shane A. Meehan, MD, of New York University, reviewed nearly 6,300 pathology reports from patients with melanomas, all referred (along with tissue samples) to their center from other institutions during 2001-2015. One or more IHC stains were used diagnostically in 871 cases during the study period, with use increasing from 5% of patients in 2001 to 25% in 2015 (P less than .0001). Usage increased gradually over time, although the number of stains used per case did not increase significantly (J Cutan Pathol. 2017 Mar;44[3]:221-7).
IHC stain use was associated with melanomas occurring on the head or neck (odds ratio = 1.6; 95% confidence interval, 1.4-1.9), acral melanomas (OR = 1.5; 95% CI 1.1-2.0) and melanomas thicker than 4 mm (OR = 2.5; 95% CI 1.7-3.6). The most common stain used in the study was Melan-A/MART-1 (melanoma antigen recognized by T cells), the most specific of the IHC markers available and the one “largely responsible for the increased incidence in overall immunostain use in our study,” the researchers wrote. “The perception that melanocytic markers, such as Melan-A, can more accurately stage melanomas, is a potential explanation for its increased usage over the duration of the study period.”
The higher use of immunostains in thicker melanomas may be because these “exhibit greater morphological heterogeneity, such as nodular, spindled and desmoplastic subtypes, that lead to additional confirmational testing,” Dr. Kim and Dr. Meehan noted. However, they cautioned that extrinsic factors, including reimbursement fees and concerns about malpractice claims, could also influence the use of IHC stains in the diagnosis of melanomas.
“While Melan-A/MART-1 is a useful adjunct for determining melanocytic density or the presence of invasion in difficult cases, its routine use on melanomas has not been validated,” the researchers wrote in their analysis. “A consensus conference delineating the appropriate use of IHC in the diagnosis of melanoma may be of value in this regard.”
Dr. Kim and Dr. Meehan also noted that while a greater proportion of the melanomas seen in the study were thick (greater than 4 mm) compared with most population-based studies, this may reflect patient management practices in which thinner melanomas are treated in outpatient centers while thicker ones get referred to tertiary care centers such as theirs.
The researchers disclosed no outside funding or conflicts of interest.
While there is little consensus on the ideal role of immunohistochemical (IHC) stains in the diagnosis of melanoma, their use increased dramatically over a 15-year period, according to results from a study.
Randie H. Kim, MD, PhD, and Shane A. Meehan, MD, of New York University, reviewed nearly 6,300 pathology reports from patients with melanomas, all referred (along with tissue samples) to their center from other institutions during 2001-2015. One or more IHC stains were used diagnostically in 871 cases during the study period, with use increasing from 5% of patients in 2001 to 25% in 2015 (P less than .0001). Usage increased gradually over time, although the number of stains used per case did not increase significantly (J Cutan Pathol. 2017 Mar;44[3]:221-7).
IHC stain use was associated with melanomas occurring on the head or neck (odds ratio = 1.6; 95% confidence interval, 1.4-1.9), acral melanomas (OR = 1.5; 95% CI 1.1-2.0) and melanomas thicker than 4 mm (OR = 2.5; 95% CI 1.7-3.6). The most common stain used in the study was Melan-A/MART-1 (melanoma antigen recognized by T cells), the most specific of the IHC markers available and the one “largely responsible for the increased incidence in overall immunostain use in our study,” the researchers wrote. “The perception that melanocytic markers, such as Melan-A, can more accurately stage melanomas, is a potential explanation for its increased usage over the duration of the study period.”
The higher use of immunostains in thicker melanomas may be because these “exhibit greater morphological heterogeneity, such as nodular, spindled and desmoplastic subtypes, that lead to additional confirmational testing,” Dr. Kim and Dr. Meehan noted. However, they cautioned that extrinsic factors, including reimbursement fees and concerns about malpractice claims, could also influence the use of IHC stains in the diagnosis of melanomas.
“While Melan-A/MART-1 is a useful adjunct for determining melanocytic density or the presence of invasion in difficult cases, its routine use on melanomas has not been validated,” the researchers wrote in their analysis. “A consensus conference delineating the appropriate use of IHC in the diagnosis of melanoma may be of value in this regard.”
Dr. Kim and Dr. Meehan also noted that while a greater proportion of the melanomas seen in the study were thick (greater than 4 mm) compared with most population-based studies, this may reflect patient management practices in which thinner melanomas are treated in outpatient centers while thicker ones get referred to tertiary care centers such as theirs.
The researchers disclosed no outside funding or conflicts of interest.
While there is little consensus on the ideal role of immunohistochemical (IHC) stains in the diagnosis of melanoma, their use increased dramatically over a 15-year period, according to results from a study.
Randie H. Kim, MD, PhD, and Shane A. Meehan, MD, of New York University, reviewed nearly 6,300 pathology reports from patients with melanomas, all referred (along with tissue samples) to their center from other institutions during 2001-2015. One or more IHC stains were used diagnostically in 871 cases during the study period, with use increasing from 5% of patients in 2001 to 25% in 2015 (P less than .0001). Usage increased gradually over time, although the number of stains used per case did not increase significantly (J Cutan Pathol. 2017 Mar;44[3]:221-7).
IHC stain use was associated with melanomas occurring on the head or neck (odds ratio = 1.6; 95% confidence interval, 1.4-1.9), acral melanomas (OR = 1.5; 95% CI 1.1-2.0) and melanomas thicker than 4 mm (OR = 2.5; 95% CI 1.7-3.6). The most common stain used in the study was Melan-A/MART-1 (melanoma antigen recognized by T cells), the most specific of the IHC markers available and the one “largely responsible for the increased incidence in overall immunostain use in our study,” the researchers wrote. “The perception that melanocytic markers, such as Melan-A, can more accurately stage melanomas, is a potential explanation for its increased usage over the duration of the study period.”
The higher use of immunostains in thicker melanomas may be because these “exhibit greater morphological heterogeneity, such as nodular, spindled and desmoplastic subtypes, that lead to additional confirmational testing,” Dr. Kim and Dr. Meehan noted. However, they cautioned that extrinsic factors, including reimbursement fees and concerns about malpractice claims, could also influence the use of IHC stains in the diagnosis of melanomas.
“While Melan-A/MART-1 is a useful adjunct for determining melanocytic density or the presence of invasion in difficult cases, its routine use on melanomas has not been validated,” the researchers wrote in their analysis. “A consensus conference delineating the appropriate use of IHC in the diagnosis of melanoma may be of value in this regard.”
Dr. Kim and Dr. Meehan also noted that while a greater proportion of the melanomas seen in the study were thick (greater than 4 mm) compared with most population-based studies, this may reflect patient management practices in which thinner melanomas are treated in outpatient centers while thicker ones get referred to tertiary care centers such as theirs.
The researchers disclosed no outside funding or conflicts of interest.
FROM THE JOURNAL OF CUTANEOUS PATHOLOGY
Key clinical point:
Major finding: One or more stains was used diagnostically in 5% of melanoma cases in 2001, compared with 25% in 2015 (P less than .0001).
Data source: A retrospective review of more than 6,000 case records referred after diagnosis to a tertiary care center during 2001-2015.
Disclosures: The researchers disclosed no outside funding or conflicts of interest.