SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.

“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.

According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”

It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.

The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).

In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”

In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).

Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.

In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.

The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”

Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”

She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”

The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”

But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”

Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).

As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.

Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.

Dr. Hladunewich reports no disclosures.

SOURCE: Kidney Week 2018, Abstract FR-OR078.

SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.

“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.

According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”

It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.

The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).

In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”

In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).

Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.

In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.

The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”

Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”

She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”

The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”

But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”

Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).

As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.

Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.

Dr. Hladunewich reports no disclosures.

SOURCE: Kidney Week 2018, Abstract FR-OR078.

SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.

“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.

According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”

It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.

The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).

In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”

In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).

Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.

In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.

The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”

Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”

She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”

The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”

But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”

Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).

As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.

Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.

Dr. Hladunewich reports no disclosures.

SOURCE: Kidney Week 2018, Abstract FR-OR078.

When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.

You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.

The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)

In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.

The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?

But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?

Consider the following two sentences.

• “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
• “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”

These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”

Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.

At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.

Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.

The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”

The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.

At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.

Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.

When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.

You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.

The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)

In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.

The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?

But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?

Consider the following two sentences.

• “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
• “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”

These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”

Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.

At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.

Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.

The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”

The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.

At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.

Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.

When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.

You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.

The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)

In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.

The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?

But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?

Consider the following two sentences.

• “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
• “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”

These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”

Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.

At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.

Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.

The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”

The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.

At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.

Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.

Doug Menuez/thinkstock

Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.

A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.

The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.

In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.

Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.

“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.

The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
 

SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.

Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.

Doug Menuez/thinkstock

Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.

A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.

The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.

In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.

Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.

“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.

The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
 

SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.

Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.

Doug Menuez/thinkstock

Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.

A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.

The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.

In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.

Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.

“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.

The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
 

SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

[email protected]

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

[email protected]

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

[email protected]

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.

Wikimedia Commons/FitzColinGerald/Creative Commons License

But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.

The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”

CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.

Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”

The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.

The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.

The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.

“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.

A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.

“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”

Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.

It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.

“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”

Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.

In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”

That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.

“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”

Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
 

[email protected]

After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.

Wikimedia Commons/FitzColinGerald/Creative Commons License

But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.

The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”

CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.

Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”

The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.

The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.

The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.

“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.

A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.

“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”

Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.

It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.

“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”

Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.

In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”

That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.

“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”

Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
 

[email protected]

After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.

Wikimedia Commons/FitzColinGerald/Creative Commons License

But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.

The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”

CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.

Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”

The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.

The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.

The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.

“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.

A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.

“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”

Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.

It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.

“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”

Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.

In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”

That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.

“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”

Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
 

[email protected]

NASHVILLE, tenn. – Antibiotic use in the first 2 years of life was associated with a small amount of weight gain by 10 years of age, but the amount is “likely clinically insignificant,” according to new data presented at Obesity Week.

Kari Oakes/MDedge News

At 10 years of age, children without chronic health conditions who received any antibiotics had an odds ratio of 1.02 for being overweight or obese; for children with complex chronic conditions, the OR was 1.07 (95% confidence intervals, 0.97-1.07 and 0.96-1.19, respectively). The findings were based on data from almost 60,000 children studied in a large, multi-institutional national cohort.

“This is good news,” said first author Sheryl Rifas-Shiman, MPH, discussing the findings during a poster session. She noted that the 10-year data from the longitudinal study are consistent with findings at the 5-year mark that had previously been reported.

The study comes against the background of a recent meta-analysis finding that children given any antibiotics before age 24 months had a higher body mass index z-score (BMI-z) in childhood than children who didn’t take antibiotics. Disruptions that antibiotics can cause in the gut microbiome have been hypothesized to promote overweight and obesity in children.

The present study was conducted using electronic medical record data from 2009-2016 drawn from institutions participating in PCORnet, a national research collaboration and clearinghouse.

The analysis dichotomized the cohort into those who, by 24 months of age, had received any antibiotics and those who received none. Ms. Rifas-Shiman and her colleagues also looked at a categorical count of the number of antibiotic prescriptions, from 0 to 4 or more.

Finally, they broke the type of antibiotics into narrow- or broad-spectrum, she said in an interview during the poster session. In order for exposure to be considered narrow-spectrum only, the analysis was limited to participants who had no broad-spectrum antibiotic exposure during the same time frame.

The study’s multivariable analysis also took into account complex chronic conditions the children may have had.

Fifty-seven percent of children received antibiotics before the age of 24 months. Patients were overall just under half (48%) female, and about half (49%) were white. Black children made up 37% of the cohort, and Hispanic children constituted 12%.

By 10 years of age, 36% of participants were overweight or obese, with BMIs at or above the 85th percentile, according to 2000 Centers for Disease Control growth charts.

There was a suggestion of a dose-response relationship for both narrow- and broad-spectrum antibiotics because only at the higher antibiotic exposures did increased BMI-z reach statistical significance. However, broad-spectrum antibiotics were not more likely than narrow-spectrum antibiotics to be associated with increased BMI-z.

Other multivariable adjustment took into account site clustering and adjusted for sex, race, ethnicity, preterm birth, asthma or infectious disease diagnoses, and corticosteroid exposure, as well as health care visits in the first 2 years of life.

Limitations of the study included the fact that it was observational, raising the potential for undetected confounders. Also, since the study looked at prescription, rather than dispensing data, there could be some exposure misclassification by which children who were classified as having taken antibiotics did not actually take them or did not take the full amount prescribed.

“Antibiotics should always be used judiciously; however, the long-term risk of childhood obesity from antibiotics in infancy appears to be small and clinically insignificant,” wrote Ms. Rifas-Shiman, of the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston.

The study was funded by an award from the Patient-Centered Outcomes Research Institute.
 

[email protected]

SOURCE: Rifas-Shiman et al. Obesity Week 2018, Poster TP-3155.

NASHVILLE, tenn. – Antibiotic use in the first 2 years of life was associated with a small amount of weight gain by 10 years of age, but the amount is “likely clinically insignificant,” according to new data presented at Obesity Week.

Kari Oakes/MDedge News

At 10 years of age, children without chronic health conditions who received any antibiotics had an odds ratio of 1.02 for being overweight or obese; for children with complex chronic conditions, the OR was 1.07 (95% confidence intervals, 0.97-1.07 and 0.96-1.19, respectively). The findings were based on data from almost 60,000 children studied in a large, multi-institutional national cohort.

“This is good news,” said first author Sheryl Rifas-Shiman, MPH, discussing the findings during a poster session. She noted that the 10-year data from the longitudinal study are consistent with findings at the 5-year mark that had previously been reported.

The study comes against the background of a recent meta-analysis finding that children given any antibiotics before age 24 months had a higher body mass index z-score (BMI-z) in childhood than children who didn’t take antibiotics. Disruptions that antibiotics can cause in the gut microbiome have been hypothesized to promote overweight and obesity in children.

The present study was conducted using electronic medical record data from 2009-2016 drawn from institutions participating in PCORnet, a national research collaboration and clearinghouse.

The analysis dichotomized the cohort into those who, by 24 months of age, had received any antibiotics and those who received none. Ms. Rifas-Shiman and her colleagues also looked at a categorical count of the number of antibiotic prescriptions, from 0 to 4 or more.

Finally, they broke the type of antibiotics into narrow- or broad-spectrum, she said in an interview during the poster session. In order for exposure to be considered narrow-spectrum only, the analysis was limited to participants who had no broad-spectrum antibiotic exposure during the same time frame.

The study’s multivariable analysis also took into account complex chronic conditions the children may have had.

Fifty-seven percent of children received antibiotics before the age of 24 months. Patients were overall just under half (48%) female, and about half (49%) were white. Black children made up 37% of the cohort, and Hispanic children constituted 12%.

By 10 years of age, 36% of participants were overweight or obese, with BMIs at or above the 85th percentile, according to 2000 Centers for Disease Control growth charts.

There was a suggestion of a dose-response relationship for both narrow- and broad-spectrum antibiotics because only at the higher antibiotic exposures did increased BMI-z reach statistical significance. However, broad-spectrum antibiotics were not more likely than narrow-spectrum antibiotics to be associated with increased BMI-z.

Other multivariable adjustment took into account site clustering and adjusted for sex, race, ethnicity, preterm birth, asthma or infectious disease diagnoses, and corticosteroid exposure, as well as health care visits in the first 2 years of life.

Limitations of the study included the fact that it was observational, raising the potential for undetected confounders. Also, since the study looked at prescription, rather than dispensing data, there could be some exposure misclassification by which children who were classified as having taken antibiotics did not actually take them or did not take the full amount prescribed.

“Antibiotics should always be used judiciously; however, the long-term risk of childhood obesity from antibiotics in infancy appears to be small and clinically insignificant,” wrote Ms. Rifas-Shiman, of the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston.

The study was funded by an award from the Patient-Centered Outcomes Research Institute.
 

[email protected]

SOURCE: Rifas-Shiman et al. Obesity Week 2018, Poster TP-3155.

NASHVILLE, tenn. – Antibiotic use in the first 2 years of life was associated with a small amount of weight gain by 10 years of age, but the amount is “likely clinically insignificant,” according to new data presented at Obesity Week.

Kari Oakes/MDedge News

At 10 years of age, children without chronic health conditions who received any antibiotics had an odds ratio of 1.02 for being overweight or obese; for children with complex chronic conditions, the OR was 1.07 (95% confidence intervals, 0.97-1.07 and 0.96-1.19, respectively). The findings were based on data from almost 60,000 children studied in a large, multi-institutional national cohort.

“This is good news,” said first author Sheryl Rifas-Shiman, MPH, discussing the findings during a poster session. She noted that the 10-year data from the longitudinal study are consistent with findings at the 5-year mark that had previously been reported.

The study comes against the background of a recent meta-analysis finding that children given any antibiotics before age 24 months had a higher body mass index z-score (BMI-z) in childhood than children who didn’t take antibiotics. Disruptions that antibiotics can cause in the gut microbiome have been hypothesized to promote overweight and obesity in children.

The present study was conducted using electronic medical record data from 2009-2016 drawn from institutions participating in PCORnet, a national research collaboration and clearinghouse.

The analysis dichotomized the cohort into those who, by 24 months of age, had received any antibiotics and those who received none. Ms. Rifas-Shiman and her colleagues also looked at a categorical count of the number of antibiotic prescriptions, from 0 to 4 or more.

Finally, they broke the type of antibiotics into narrow- or broad-spectrum, she said in an interview during the poster session. In order for exposure to be considered narrow-spectrum only, the analysis was limited to participants who had no broad-spectrum antibiotic exposure during the same time frame.

The study’s multivariable analysis also took into account complex chronic conditions the children may have had.

Fifty-seven percent of children received antibiotics before the age of 24 months. Patients were overall just under half (48%) female, and about half (49%) were white. Black children made up 37% of the cohort, and Hispanic children constituted 12%.

By 10 years of age, 36% of participants were overweight or obese, with BMIs at or above the 85th percentile, according to 2000 Centers for Disease Control growth charts.

There was a suggestion of a dose-response relationship for both narrow- and broad-spectrum antibiotics because only at the higher antibiotic exposures did increased BMI-z reach statistical significance. However, broad-spectrum antibiotics were not more likely than narrow-spectrum antibiotics to be associated with increased BMI-z.

Other multivariable adjustment took into account site clustering and adjusted for sex, race, ethnicity, preterm birth, asthma or infectious disease diagnoses, and corticosteroid exposure, as well as health care visits in the first 2 years of life.

Limitations of the study included the fact that it was observational, raising the potential for undetected confounders. Also, since the study looked at prescription, rather than dispensing data, there could be some exposure misclassification by which children who were classified as having taken antibiotics did not actually take them or did not take the full amount prescribed.

“Antibiotics should always be used judiciously; however, the long-term risk of childhood obesity from antibiotics in infancy appears to be small and clinically insignificant,” wrote Ms. Rifas-Shiman, of the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston.

The study was funded by an award from the Patient-Centered Outcomes Research Institute.
 

[email protected]

SOURCE: Rifas-Shiman et al. Obesity Week 2018, Poster TP-3155.

BERLIN – Demyelinating diseases appear to disrupt white matter development in children, slowing the trajectory of brain growth to almost unmeasurable levels, based on results from a single-center comparison study of 213 individuals.

While children with multiple sclerosis (MS) showed the most severe slowing, even a single demyelinating event slowed white matter growth, Robert A. Brown, PhD, said at the annual congress of the European Committees for Treatment and Research in Multiple Sclerosis.

Dr. Brown of the Montreal Neurological Institute at McGill University, Montreal, employed a signal mass correction of consecutive brain MRIs enhanced with magnetization transfer. Magnetization transfer ratio (MTR) quantifies myelin more effectively than does other imaging enhancement modalities, Dr. Brown said.

“It labels the macromolecules of myelin and correlates almost perfectly with Luxol fast blue stain on histology,” he said. And by measuring myelin instead of whole-brain volume, MTR sidesteps the confounders of inflammation and edema. “When tissue swells, the water dilutes the myelin. MRI is really sensitive to density, so dilution with water lowers that signal.”

But MTR isn’t failsafe either, he said, especially in teens. “A cautionary note: In healthy adolescents, white matter MTR can actually decrease, not increase, not because they are losing myelin but because the axons in brain tissue are growing so fast that they outstrip the production of new myelin. So, we can get another dilution effect here, except that instead of water, axons are diluting the myelin. We have to take that into account when using MTR.”

A volume-corrected MTR calculates both mass and volume to give what Dr. Brown termed signal mass. “We have demonstrated previously that signal mass is about twice as powerful as volume change alone for measuring the differences [in brain volume] between adults with MS and healthy controls.”

The study he presented at ECTRIMS used this technique to examine the trajectory of white matter change in a cohort of children from the Canadian Pediatric Demyelinating Disease Study who were all scanned at the same site in the same center. He compared brain volume at baseline and 1 year in 102 children with a monophasic demyelinating disease, 87 with MS, and 24 healthy, age-matched controls.

The children with MS were a median of about 17 years old at baseline, while those with a monophasic event and healthy controls were a median of about 12 years old. Median follow-up was 1 year in the healthy controls, 2 years in the MS cohort, and 4 years in the monophasic group. The investigators adjusted their comparisons for sex, since both bioavailable testosterone and androgen-receptor activity correlate with decreased MTR in young men. This doesn’t mean, though, that testosterone decreases myelination. Rather, it’s postulated that testosterone increases axonal caliber, which would decrease the number of neurons in each imaging voxel and, thus, the MTR signal (J Neurosci. 2008 Sep 17;28[38]:9519-24).

In the volume-only assessment, white matter in healthy controls increased at a rate of about 0.5% per year. White matter growth was about 0.2% per year in children with monophasic demyelination, which was significantly lower than in healthy controls.

“The MS children had no white matter growth that we could measure,” with an annual change of about 0.01%, Dr. Brown said. “It looks like a failure of normal development and was significantly lower than what we saw in the children with a demyelination event.”

MTR showed the expected age-associated decreases, which were highest among those with MS: –0.8% per year in healthy controls, –0.6% per year in those with a monophasic event, and –0.9% per year in those with MS.

The signal mass change showed the whole picture, Dr. Brown said. Signal mass declined 0.3% per year in healthy controls, 0.5% per year in the monophasic group, and 0.9% per year in the MS group – a significantly worse trajectory than either the control subjects or those with a monophasic event.

“Signal mass puts it all together and gives us the total picture of tissue loss, with quite severe loss in children with MS. It seems as though both monophasic insult and pediatric-onset MS disrupt brain development.”

Dr. Brown has been a consultant for NeuroRx Research and Biogen.

[email protected]

SOURCE: Brown RA et al. Mult Scler. 2018;24(S2):27-8, Abstract 63.

BERLIN – Demyelinating diseases appear to disrupt white matter development in children, slowing the trajectory of brain growth to almost unmeasurable levels, based on results from a single-center comparison study of 213 individuals.

While children with multiple sclerosis (MS) showed the most severe slowing, even a single demyelinating event slowed white matter growth, Robert A. Brown, PhD, said at the annual congress of the European Committees for Treatment and Research in Multiple Sclerosis.

Dr. Brown of the Montreal Neurological Institute at McGill University, Montreal, employed a signal mass correction of consecutive brain MRIs enhanced with magnetization transfer. Magnetization transfer ratio (MTR) quantifies myelin more effectively than does other imaging enhancement modalities, Dr. Brown said.

“It labels the macromolecules of myelin and correlates almost perfectly with Luxol fast blue stain on histology,” he said. And by measuring myelin instead of whole-brain volume, MTR sidesteps the confounders of inflammation and edema. “When tissue swells, the water dilutes the myelin. MRI is really sensitive to density, so dilution with water lowers that signal.”

But MTR isn’t failsafe either, he said, especially in teens. “A cautionary note: In healthy adolescents, white matter MTR can actually decrease, not increase, not because they are losing myelin but because the axons in brain tissue are growing so fast that they outstrip the production of new myelin. So, we can get another dilution effect here, except that instead of water, axons are diluting the myelin. We have to take that into account when using MTR.”

A volume-corrected MTR calculates both mass and volume to give what Dr. Brown termed signal mass. “We have demonstrated previously that signal mass is about twice as powerful as volume change alone for measuring the differences [in brain volume] between adults with MS and healthy controls.”

The study he presented at ECTRIMS used this technique to examine the trajectory of white matter change in a cohort of children from the Canadian Pediatric Demyelinating Disease Study who were all scanned at the same site in the same center. He compared brain volume at baseline and 1 year in 102 children with a monophasic demyelinating disease, 87 with MS, and 24 healthy, age-matched controls.

The children with MS were a median of about 17 years old at baseline, while those with a monophasic event and healthy controls were a median of about 12 years old. Median follow-up was 1 year in the healthy controls, 2 years in the MS cohort, and 4 years in the monophasic group. The investigators adjusted their comparisons for sex, since both bioavailable testosterone and androgen-receptor activity correlate with decreased MTR in young men. This doesn’t mean, though, that testosterone decreases myelination. Rather, it’s postulated that testosterone increases axonal caliber, which would decrease the number of neurons in each imaging voxel and, thus, the MTR signal (J Neurosci. 2008 Sep 17;28[38]:9519-24).

In the volume-only assessment, white matter in healthy controls increased at a rate of about 0.5% per year. White matter growth was about 0.2% per year in children with monophasic demyelination, which was significantly lower than in healthy controls.

“The MS children had no white matter growth that we could measure,” with an annual change of about 0.01%, Dr. Brown said. “It looks like a failure of normal development and was significantly lower than what we saw in the children with a demyelination event.”

MTR showed the expected age-associated decreases, which were highest among those with MS: –0.8% per year in healthy controls, –0.6% per year in those with a monophasic event, and –0.9% per year in those with MS.

The signal mass change showed the whole picture, Dr. Brown said. Signal mass declined 0.3% per year in healthy controls, 0.5% per year in the monophasic group, and 0.9% per year in the MS group – a significantly worse trajectory than either the control subjects or those with a monophasic event.

“Signal mass puts it all together and gives us the total picture of tissue loss, with quite severe loss in children with MS. It seems as though both monophasic insult and pediatric-onset MS disrupt brain development.”

Dr. Brown has been a consultant for NeuroRx Research and Biogen.

[email protected]

SOURCE: Brown RA et al. Mult Scler. 2018;24(S2):27-8, Abstract 63.

BERLIN – Demyelinating diseases appear to disrupt white matter development in children, slowing the trajectory of brain growth to almost unmeasurable levels, based on results from a single-center comparison study of 213 individuals.

While children with multiple sclerosis (MS) showed the most severe slowing, even a single demyelinating event slowed white matter growth, Robert A. Brown, PhD, said at the annual congress of the European Committees for Treatment and Research in Multiple Sclerosis.

Dr. Brown of the Montreal Neurological Institute at McGill University, Montreal, employed a signal mass correction of consecutive brain MRIs enhanced with magnetization transfer. Magnetization transfer ratio (MTR) quantifies myelin more effectively than does other imaging enhancement modalities, Dr. Brown said.

“It labels the macromolecules of myelin and correlates almost perfectly with Luxol fast blue stain on histology,” he said. And by measuring myelin instead of whole-brain volume, MTR sidesteps the confounders of inflammation and edema. “When tissue swells, the water dilutes the myelin. MRI is really sensitive to density, so dilution with water lowers that signal.”

But MTR isn’t failsafe either, he said, especially in teens. “A cautionary note: In healthy adolescents, white matter MTR can actually decrease, not increase, not because they are losing myelin but because the axons in brain tissue are growing so fast that they outstrip the production of new myelin. So, we can get another dilution effect here, except that instead of water, axons are diluting the myelin. We have to take that into account when using MTR.”

A volume-corrected MTR calculates both mass and volume to give what Dr. Brown termed signal mass. “We have demonstrated previously that signal mass is about twice as powerful as volume change alone for measuring the differences [in brain volume] between adults with MS and healthy controls.”

The study he presented at ECTRIMS used this technique to examine the trajectory of white matter change in a cohort of children from the Canadian Pediatric Demyelinating Disease Study who were all scanned at the same site in the same center. He compared brain volume at baseline and 1 year in 102 children with a monophasic demyelinating disease, 87 with MS, and 24 healthy, age-matched controls.

The children with MS were a median of about 17 years old at baseline, while those with a monophasic event and healthy controls were a median of about 12 years old. Median follow-up was 1 year in the healthy controls, 2 years in the MS cohort, and 4 years in the monophasic group. The investigators adjusted their comparisons for sex, since both bioavailable testosterone and androgen-receptor activity correlate with decreased MTR in young men. This doesn’t mean, though, that testosterone decreases myelination. Rather, it’s postulated that testosterone increases axonal caliber, which would decrease the number of neurons in each imaging voxel and, thus, the MTR signal (J Neurosci. 2008 Sep 17;28[38]:9519-24).

In the volume-only assessment, white matter in healthy controls increased at a rate of about 0.5% per year. White matter growth was about 0.2% per year in children with monophasic demyelination, which was significantly lower than in healthy controls.

“The MS children had no white matter growth that we could measure,” with an annual change of about 0.01%, Dr. Brown said. “It looks like a failure of normal development and was significantly lower than what we saw in the children with a demyelination event.”

MTR showed the expected age-associated decreases, which were highest among those with MS: –0.8% per year in healthy controls, –0.6% per year in those with a monophasic event, and –0.9% per year in those with MS.

The signal mass change showed the whole picture, Dr. Brown said. Signal mass declined 0.3% per year in healthy controls, 0.5% per year in the monophasic group, and 0.9% per year in the MS group – a significantly worse trajectory than either the control subjects or those with a monophasic event.

“Signal mass puts it all together and gives us the total picture of tissue loss, with quite severe loss in children with MS. It seems as though both monophasic insult and pediatric-onset MS disrupt brain development.”

Dr. Brown has been a consultant for NeuroRx Research and Biogen.

[email protected]

SOURCE: Brown RA et al. Mult Scler. 2018;24(S2):27-8, Abstract 63.

In October of this year, the first ever Integrative Dermatology Symposium was held in Sacramento, Calif., bringing together board-certified dermatologists, and practitioners of Ayurvedic, Naturopathic, and traditional Chinese medicine (TCM), in one place. This was the first time in the United States that practitioners from these different areas of medicine were brought together to discuss and learn different approaches to skin care and treatment of dermatologic diseases.

Daniel Schwen/CCA-SA 3.0

Of all the medical specialties, it is presumed that dermatology is the most inherently holistic. By examining the hair, skin, and nails, we are able to diagnose internal organ diseases such as liver failure (jaundice, veins on stomach), thyroid disease (madarosis), sarcoidosis, and infectious diseases (cutaneous manifestations of HIV), diabetes (acanthosis nigricans, tripe palm), polycystic ovary syndrome (acne, hirsutism), and porphyria, just to name a few. We are also able to treat cutaneous conditions, such as psoriasis, with biologic medications, treatment that in turn, also benefits internal manifestations such as joint, cardiovascular, and metabolic disease. In TCM and Ayurveda, the skin, hair, body type, and tongue can also be analyzed to diagnose and treat disease.

Salves and skin care routines that would be considered natural or holistic have been “prescribed” by Western dermatologists with an MD license for many years. Most medicines initially come from nature, and it is only in the past century, with the boom in the pharmaceutical industry and development of synthetic prescription medications, that people have forgotten this. Some of this boom has been needed to treat enormous populations, as natural resources can be scarce, and in some cases, only an extract of the plant may be needed for treatment, where other elements may be ineffective or even harmful.

Domeboro solution, Epsom salt soaks, and wet to dry soaks are used to draw out and treat infections. Bleach baths are often used to decrease bacterial load and calm inflammation when treating eczema. In Mohs surgery, Fredrick Mohs initially used a zinc chloride paste on nonmelanoma skin cancers in between stages, before frozen section processing and cosmetic reconstruction made Mohs what it is today. In the days of Hippocrates, food was medicine. If you were “red in the face” your blood was deemed too acidic and alkaline-forming foods or “cold foods” were given. This has now again come full circle with rosacea and evidence supporting a link between disease flares or improvement related to foods and the gut microbiome.

On a photography trip to Wyoming, I learned how Native Americans in the United States wiped the white powder from the bark of aspen trees on their skin and used it as sunscreen. In Mongolia, I learned how fat from a sheep’s bottom was used in beauty skin care routines. It is from native and nomadic people that we can often learn how effective natural methods can be used, especially in cases where the treatment regimens may not be written down. With Ayurveda and TCM, we are lucky that textbooks thousands of years old and professors and schools are available to educate us about these ancient practices.

The rediscovery of ancient treatments through the study of ethnobotany, Ayurveda, and TCM has been fascinating, as most of these approaches focus not just on the skin, but on treating the patient as a whole, inside and out (often depending on the discipline treating mind, body, and spirit), with the effects ultimately benefiting the skin. With the many advances in Western medicine over the past 2,000 years, starting with Hippocrates, it will be interesting to see how we, in the field of dermatology, can still learn from and potentially integrate medicine that originated 3,000-5,000 plus years ago in Ayurveda and 2,000-plus years ago in TCM that is still practiced today. In the future, we hope to have more columns about these specialties and how they are used in skin and beauty.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

In October of this year, the first ever Integrative Dermatology Symposium was held in Sacramento, Calif., bringing together board-certified dermatologists, and practitioners of Ayurvedic, Naturopathic, and traditional Chinese medicine (TCM), in one place. This was the first time in the United States that practitioners from these different areas of medicine were brought together to discuss and learn different approaches to skin care and treatment of dermatologic diseases.

Daniel Schwen/CCA-SA 3.0

Of all the medical specialties, it is presumed that dermatology is the most inherently holistic. By examining the hair, skin, and nails, we are able to diagnose internal organ diseases such as liver failure (jaundice, veins on stomach), thyroid disease (madarosis), sarcoidosis, and infectious diseases (cutaneous manifestations of HIV), diabetes (acanthosis nigricans, tripe palm), polycystic ovary syndrome (acne, hirsutism), and porphyria, just to name a few. We are also able to treat cutaneous conditions, such as psoriasis, with biologic medications, treatment that in turn, also benefits internal manifestations such as joint, cardiovascular, and metabolic disease. In TCM and Ayurveda, the skin, hair, body type, and tongue can also be analyzed to diagnose and treat disease.

Salves and skin care routines that would be considered natural or holistic have been “prescribed” by Western dermatologists with an MD license for many years. Most medicines initially come from nature, and it is only in the past century, with the boom in the pharmaceutical industry and development of synthetic prescription medications, that people have forgotten this. Some of this boom has been needed to treat enormous populations, as natural resources can be scarce, and in some cases, only an extract of the plant may be needed for treatment, where other elements may be ineffective or even harmful.

Domeboro solution, Epsom salt soaks, and wet to dry soaks are used to draw out and treat infections. Bleach baths are often used to decrease bacterial load and calm inflammation when treating eczema. In Mohs surgery, Fredrick Mohs initially used a zinc chloride paste on nonmelanoma skin cancers in between stages, before frozen section processing and cosmetic reconstruction made Mohs what it is today. In the days of Hippocrates, food was medicine. If you were “red in the face” your blood was deemed too acidic and alkaline-forming foods or “cold foods” were given. This has now again come full circle with rosacea and evidence supporting a link between disease flares or improvement related to foods and the gut microbiome.

On a photography trip to Wyoming, I learned how Native Americans in the United States wiped the white powder from the bark of aspen trees on their skin and used it as sunscreen. In Mongolia, I learned how fat from a sheep’s bottom was used in beauty skin care routines. It is from native and nomadic people that we can often learn how effective natural methods can be used, especially in cases where the treatment regimens may not be written down. With Ayurveda and TCM, we are lucky that textbooks thousands of years old and professors and schools are available to educate us about these ancient practices.

The rediscovery of ancient treatments through the study of ethnobotany, Ayurveda, and TCM has been fascinating, as most of these approaches focus not just on the skin, but on treating the patient as a whole, inside and out (often depending on the discipline treating mind, body, and spirit), with the effects ultimately benefiting the skin. With the many advances in Western medicine over the past 2,000 years, starting with Hippocrates, it will be interesting to see how we, in the field of dermatology, can still learn from and potentially integrate medicine that originated 3,000-5,000 plus years ago in Ayurveda and 2,000-plus years ago in TCM that is still practiced today. In the future, we hope to have more columns about these specialties and how they are used in skin and beauty.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

In October of this year, the first ever Integrative Dermatology Symposium was held in Sacramento, Calif., bringing together board-certified dermatologists, and practitioners of Ayurvedic, Naturopathic, and traditional Chinese medicine (TCM), in one place. This was the first time in the United States that practitioners from these different areas of medicine were brought together to discuss and learn different approaches to skin care and treatment of dermatologic diseases.

Daniel Schwen/CCA-SA 3.0

Of all the medical specialties, it is presumed that dermatology is the most inherently holistic. By examining the hair, skin, and nails, we are able to diagnose internal organ diseases such as liver failure (jaundice, veins on stomach), thyroid disease (madarosis), sarcoidosis, and infectious diseases (cutaneous manifestations of HIV), diabetes (acanthosis nigricans, tripe palm), polycystic ovary syndrome (acne, hirsutism), and porphyria, just to name a few. We are also able to treat cutaneous conditions, such as psoriasis, with biologic medications, treatment that in turn, also benefits internal manifestations such as joint, cardiovascular, and metabolic disease. In TCM and Ayurveda, the skin, hair, body type, and tongue can also be analyzed to diagnose and treat disease.

Salves and skin care routines that would be considered natural or holistic have been “prescribed” by Western dermatologists with an MD license for many years. Most medicines initially come from nature, and it is only in the past century, with the boom in the pharmaceutical industry and development of synthetic prescription medications, that people have forgotten this. Some of this boom has been needed to treat enormous populations, as natural resources can be scarce, and in some cases, only an extract of the plant may be needed for treatment, where other elements may be ineffective or even harmful.

Domeboro solution, Epsom salt soaks, and wet to dry soaks are used to draw out and treat infections. Bleach baths are often used to decrease bacterial load and calm inflammation when treating eczema. In Mohs surgery, Fredrick Mohs initially used a zinc chloride paste on nonmelanoma skin cancers in between stages, before frozen section processing and cosmetic reconstruction made Mohs what it is today. In the days of Hippocrates, food was medicine. If you were “red in the face” your blood was deemed too acidic and alkaline-forming foods or “cold foods” were given. This has now again come full circle with rosacea and evidence supporting a link between disease flares or improvement related to foods and the gut microbiome.

On a photography trip to Wyoming, I learned how Native Americans in the United States wiped the white powder from the bark of aspen trees on their skin and used it as sunscreen. In Mongolia, I learned how fat from a sheep’s bottom was used in beauty skin care routines. It is from native and nomadic people that we can often learn how effective natural methods can be used, especially in cases where the treatment regimens may not be written down. With Ayurveda and TCM, we are lucky that textbooks thousands of years old and professors and schools are available to educate us about these ancient practices.

The rediscovery of ancient treatments through the study of ethnobotany, Ayurveda, and TCM has been fascinating, as most of these approaches focus not just on the skin, but on treating the patient as a whole, inside and out (often depending on the discipline treating mind, body, and spirit), with the effects ultimately benefiting the skin. With the many advances in Western medicine over the past 2,000 years, starting with Hippocrates, it will be interesting to see how we, in the field of dermatology, can still learn from and potentially integrate medicine that originated 3,000-5,000 plus years ago in Ayurveda and 2,000-plus years ago in TCM that is still practiced today. In the future, we hope to have more columns about these specialties and how they are used in skin and beauty.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.