User login
M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
SGLT inhibitor still possible for T1DM, despite FDA committee vote
on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.
In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.
The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.
DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).
“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.
Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.
“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.
Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”
Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.
A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.
“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.
Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.
Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.
Dr. Wilson and Dr. Low Wang did not have any disclosures.
on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.
In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.
The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.
DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).
“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.
Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.
“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.
Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”
Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.
A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.
“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.
Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.
Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.
Dr. Wilson and Dr. Low Wang did not have any disclosures.
on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.
In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.
The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.
DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).
“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.
Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.
“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.
Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”
Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.
A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.
“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.
Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.
Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.
Dr. Wilson and Dr. Low Wang did not have any disclosures.
TAPs top epidurals in ventral hernia repair
, according to a review of 246 cases at the Greenville Health System, in South Carolina.
“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.
Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.
Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.
Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.
Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).
There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.
The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.
Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.
Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.
The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.
There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.
No funding was reported, and the investigators didn’t have any relevant disclosures.
SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017
, according to a review of 246 cases at the Greenville Health System, in South Carolina.
“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.
Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.
Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.
Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.
Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).
There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.
The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.
Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.
Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.
The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.
There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.
No funding was reported, and the investigators didn’t have any relevant disclosures.
SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017
, according to a review of 246 cases at the Greenville Health System, in South Carolina.
“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.
Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.
Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.
Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.
Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).
There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.
The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.
Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.
Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.
The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.
There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.
No funding was reported, and the investigators didn’t have any relevant disclosures.
SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Key clinical point: TAP blocks are better than epidurals for pain control after ventral hernia repair.
Major finding: Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1.
Study details: Review of 246 repairs
Disclosures: No funding was reported, and the investigators didn’t have any relevant disclosures.
Source: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017
FDA labeling templates smooth way for OTC naloxone
Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.
“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.
There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.
As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.
Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.
In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”
Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.
“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.
There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.
As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.
Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.
In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”
Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.
“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.
There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.
As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.
Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.
In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”
MMF proves viable as alternative option in moderate ANCA-associated vasculitis
Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.
“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.
“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.
Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”
The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.
They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m2 were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.
The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.
Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.
More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).
There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).
Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.
After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.
Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.
The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.
SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.
We sometimes encounter patients for whom access to rituximab is a problem, for financial, logistical, or tolerability reasons. Also, some patients are really reluctant about an infusion, and there is still some skittishness about rituximab. I have had some patients who, despite my having strongly reiterated how rare progressive multifocal leukoencephalopathy is, have been unable to get past the fact that that’s in the package insert. It’s helpful to me as a clinician to know that mycophenolate is something we can turn to in these situations. As I discuss the ups and down of different potential strategies with patients, this is something that can be part of the discussion.
This was a really well done study, and they were honest about the limitations. They excluded patients with the most severe disease, so you are still not talking about your patients on dialysis getting mycophenolate. Also, there are questions in terms of it’s not being as effective at sustaining remission, but that’s a bridge you can cross once they are in remission, in terms of how vigilant you are about follow-up. You also can re-induce remission with mycophenolate if you have to.
Robert F. Spiera, MD, is director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York. He had no relevant disclosures, and is on the editorial advisory board of MDedge Rheumatology.
We sometimes encounter patients for whom access to rituximab is a problem, for financial, logistical, or tolerability reasons. Also, some patients are really reluctant about an infusion, and there is still some skittishness about rituximab. I have had some patients who, despite my having strongly reiterated how rare progressive multifocal leukoencephalopathy is, have been unable to get past the fact that that’s in the package insert. It’s helpful to me as a clinician to know that mycophenolate is something we can turn to in these situations. As I discuss the ups and down of different potential strategies with patients, this is something that can be part of the discussion.
This was a really well done study, and they were honest about the limitations. They excluded patients with the most severe disease, so you are still not talking about your patients on dialysis getting mycophenolate. Also, there are questions in terms of it’s not being as effective at sustaining remission, but that’s a bridge you can cross once they are in remission, in terms of how vigilant you are about follow-up. You also can re-induce remission with mycophenolate if you have to.
Robert F. Spiera, MD, is director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York. He had no relevant disclosures, and is on the editorial advisory board of MDedge Rheumatology.
We sometimes encounter patients for whom access to rituximab is a problem, for financial, logistical, or tolerability reasons. Also, some patients are really reluctant about an infusion, and there is still some skittishness about rituximab. I have had some patients who, despite my having strongly reiterated how rare progressive multifocal leukoencephalopathy is, have been unable to get past the fact that that’s in the package insert. It’s helpful to me as a clinician to know that mycophenolate is something we can turn to in these situations. As I discuss the ups and down of different potential strategies with patients, this is something that can be part of the discussion.
This was a really well done study, and they were honest about the limitations. They excluded patients with the most severe disease, so you are still not talking about your patients on dialysis getting mycophenolate. Also, there are questions in terms of it’s not being as effective at sustaining remission, but that’s a bridge you can cross once they are in remission, in terms of how vigilant you are about follow-up. You also can re-induce remission with mycophenolate if you have to.
Robert F. Spiera, MD, is director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York. He had no relevant disclosures, and is on the editorial advisory board of MDedge Rheumatology.
Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.
“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.
“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.
Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”
The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.
They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m2 were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.
The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.
Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.
More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).
There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).
Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.
After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.
Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.
The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.
SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.
Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.
“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.
“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.
Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”
The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.
They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m2 were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.
The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.
Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.
More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).
There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).
Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.
After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.
Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.
The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.
SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Overall, 47 patients in the in the MMF group (67%), including 1 child, reached remission by 6 months, versus 43 subjects (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% CI, –7.5% to 19%), which established noninferiority.
Study details: Randomized, multisite trial with 140 patients.
Disclosures: The Cambridge University Hospitals NHS Foundation Trust sponsored the study. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, and ChemoCentryx, which is owned in part by Vifor.
Source: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.
Anti-TNFs slow SIJ damage in early axial spondyloarthritis
Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.
They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).
In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.
The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.
Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.
“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.
Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.
Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.
The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”
Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.
The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.
SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786
Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.
They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).
In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.
The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.
Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.
“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.
Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.
Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.
The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”
Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.
The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.
SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786
Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.
They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).
In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.
The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.
Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.
“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.
Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.
Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.
The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”
Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.
The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.
SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6.
Study details: Review of 42 patients with early disease.
Disclosures: The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.
Source: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786
Too much, too little sleep linked to atherosclerosis
in healthy middle-aged men and women in a Spanish investigation of bank employees.
“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.
Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.
The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.
The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.
After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.
LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.
Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.
Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.
The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.
SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.
This study extends the published reports on sleep duration and vascular disease to an early middle-aged cohort by using an objective measure of sleep duration and sensitive measures of atherosclerosis in multiple vascular territories.
Ultimately, studies of sleep extension are needed to determine whether modification of sleep behaviors will improve vascular health outcomes. The potentially enormous impact of sleep deprivation and disruption on population health, reinforced by the present study, is ample justification for such trials, which are needed to place sleep with confidence alongside diet and exercise as a key pillar of a healthy lifestyle.
However, both hypertension and diabetes were more common in the group sleeping fewer than 6 hours per night, but neither blood pressure nor glucose metabolism was assessed with sufficiently comprehensive measures to explore these factors as potential effect mediators.
More importantly, the causes of short sleep duration and sleep fragmentation in this cohort are unknown. It is unclear to what extent short sleep duration in this cohort reflects voluntary behaviors that limit time available for sleep versus insomnia. Insomnia is itself associated with increased risk of vascular disease.
Deepak Bhatt , MD, professor of cardiovascular medicine, and Daniel Gottlieb , MD, an associate professor of medicine at Harvard Medical School, Boston, made these comments in an accompanying editorial ( J Am Coll Cardiol. 2019 Jan 14;73[2]:145-7 ). Dr. Gottlieb is also the director of the Boston Veterans Affairs Sleep Disorders Center. Dr. Bhatt reported research funding and income from a number of companies, including Abbott, Boehringer Ingelheim, and Medtronic.
This study extends the published reports on sleep duration and vascular disease to an early middle-aged cohort by using an objective measure of sleep duration and sensitive measures of atherosclerosis in multiple vascular territories.
Ultimately, studies of sleep extension are needed to determine whether modification of sleep behaviors will improve vascular health outcomes. The potentially enormous impact of sleep deprivation and disruption on population health, reinforced by the present study, is ample justification for such trials, which are needed to place sleep with confidence alongside diet and exercise as a key pillar of a healthy lifestyle.
However, both hypertension and diabetes were more common in the group sleeping fewer than 6 hours per night, but neither blood pressure nor glucose metabolism was assessed with sufficiently comprehensive measures to explore these factors as potential effect mediators.
More importantly, the causes of short sleep duration and sleep fragmentation in this cohort are unknown. It is unclear to what extent short sleep duration in this cohort reflects voluntary behaviors that limit time available for sleep versus insomnia. Insomnia is itself associated with increased risk of vascular disease.
Deepak Bhatt , MD, professor of cardiovascular medicine, and Daniel Gottlieb , MD, an associate professor of medicine at Harvard Medical School, Boston, made these comments in an accompanying editorial ( J Am Coll Cardiol. 2019 Jan 14;73[2]:145-7 ). Dr. Gottlieb is also the director of the Boston Veterans Affairs Sleep Disorders Center. Dr. Bhatt reported research funding and income from a number of companies, including Abbott, Boehringer Ingelheim, and Medtronic.
This study extends the published reports on sleep duration and vascular disease to an early middle-aged cohort by using an objective measure of sleep duration and sensitive measures of atherosclerosis in multiple vascular territories.
Ultimately, studies of sleep extension are needed to determine whether modification of sleep behaviors will improve vascular health outcomes. The potentially enormous impact of sleep deprivation and disruption on population health, reinforced by the present study, is ample justification for such trials, which are needed to place sleep with confidence alongside diet and exercise as a key pillar of a healthy lifestyle.
However, both hypertension and diabetes were more common in the group sleeping fewer than 6 hours per night, but neither blood pressure nor glucose metabolism was assessed with sufficiently comprehensive measures to explore these factors as potential effect mediators.
More importantly, the causes of short sleep duration and sleep fragmentation in this cohort are unknown. It is unclear to what extent short sleep duration in this cohort reflects voluntary behaviors that limit time available for sleep versus insomnia. Insomnia is itself associated with increased risk of vascular disease.
Deepak Bhatt , MD, professor of cardiovascular medicine, and Daniel Gottlieb , MD, an associate professor of medicine at Harvard Medical School, Boston, made these comments in an accompanying editorial ( J Am Coll Cardiol. 2019 Jan 14;73[2]:145-7 ). Dr. Gottlieb is also the director of the Boston Veterans Affairs Sleep Disorders Center. Dr. Bhatt reported research funding and income from a number of companies, including Abbott, Boehringer Ingelheim, and Medtronic.
in healthy middle-aged men and women in a Spanish investigation of bank employees.
“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.
Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.
The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.
The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.
After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.
LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.
Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.
Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.
The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.
SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.
in healthy middle-aged men and women in a Spanish investigation of bank employees.
“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.
Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.
The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.
The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.
After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.
LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.
Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.
Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.
The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.
SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Even among healthy men and women, both too much and too little sleep are associated with atherosclerosis.
Major finding: Sleeping less than 6 hours a night was independently associated with a higher noncardiac atherosclerotic burden (OR ,1.27; 95% CI, 1.06-1.52; P = .008)
Study details: Spanish study of 3,974 bank employees.
Disclosures: The work was funded by CNIC and Banco Santander, among others. The study lead had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.
Source: Domínguez F et al. J Am Coll Cardiol. 2019;73:134-44.
Secondhand vaping aerosols linked to childhood asthma exacerbations
Just like exposure to secondhand smoke, , according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.
Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.
Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).
“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.
About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.
The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.
Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.
Just like exposure to secondhand smoke, , according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.
Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.
Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).
“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.
About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.
The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.
Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.
Just like exposure to secondhand smoke, , according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.
Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.
Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).
“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.
About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.
The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.
Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.
FROM CHEST®
Key clinical point: It’s important to screen asthmatic children for exposure to secondhand vaping aerosols, and minimize exposure.
Major finding: Secondhand aerosols increased the odds of an asthma attack 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves.
Study details: Analysis of 11,830 children with asthma in the 2016 Florida Youth Tobacco survey.
Disclosures: The work was funded by the National Institutes of Health. The investigators had no disclosures.
Source: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.
Heberden’s nodes linked to knee OA progression
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Heberden’s nodes may be an indicator of knee OA progression.
Major finding: There was more periarticular bone area expansion among patients with Heberden’s nodes at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83).
Study details: A substudy of 575 participants in the Osteoarthritis Initiative cohort
Disclosures: There was no external funding, and the investigators reported no disclosures.
Source: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
Gender, racial, socioeconomic differences found in obesity-depression link
Association holds for white women across income levels, black men with incomes of $100,000 or higher.
Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.
“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.
The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m2 or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.
A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.
For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).
The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.
Dr. Bell and her associates wrote.
As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.
The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.
Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.
The study had no financial disclosures, and the investigators reported having no conflicts of interest.
SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.
Association holds for white women across income levels, black men with incomes of $100,000 or higher.
Association holds for white women across income levels, black men with incomes of $100,000 or higher.
Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.
“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.
The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m2 or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.
A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.
For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).
The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.
Dr. Bell and her associates wrote.
As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.
The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.
Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.
The study had no financial disclosures, and the investigators reported having no conflicts of interest.
SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.
Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.
“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.
The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m2 or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.
A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.
For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).
The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.
Dr. Bell and her associates wrote.
As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.
The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.
Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.
The study had no financial disclosures, and the investigators reported having no conflicts of interest.
SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.
FROM PREVENTIVE MEDICINE
Osteomyelitis amputation risk linked to comorbidity burden
BOSTON – The higher the comorbidity burden, the greater the likelihood that osteomyelitis will lead to amputation within 2 years, according to a review of 1,186 adult osteomyelitis patients at the University of Michigan, Ann Arbor.
The limb amputation incidence was 7.2% over 2 years in patients with no comorbidities, 21.4% among patients with heart failure, 36.1% in patients with diabetes, and 36.7% among those with peripheral vascular disease (PVD).
The 2-year incidence marched steadily upward with combined comorbidities to 47.4% in patients with diabetes and heart failure; 64.5% in patients with diabetes and PVD; and 75.0% in patients with diabetes, heart failure, and PVD.
“What this means is that looking at diabetes versus no diabetes alone is not sufficient to gauge the risk of amputation. We have to look at the patient’s comorbidity profile as a whole; greater comorbidity burden and different combinations of comorbidities [increase] amputation incidence, but there’s considerable risk [7.2%] even among otherwise healthy patients,” said lead investigator Toby Keeney-Bonthrone, a medical student at the university.
The ultimate goal of the work is to develop an osteomyelitis amputation risk calculator for physicians and patients to improve decision making, validated by nationwide data. “The question is if some patients would benefit from [an earlier,] more prophylactic amputation. Would it be better to just take off the limb and be done with it, and would that decrease overall morbidity?” he said at the annual clinical congress of the American College of Surgeons.
“We often find ourselves reacting to osteomyelitis as it progresses. I think patients deserve a better deal than that. They deserve for us to think one or two steps ahead,” Mr. Keeney-Bonthrone said.
The immediate goal of the study was to fill the data gap on long-term osteomyelitis outcomes, something that hasn’t been addressed much in the literature. The team reviewed adult patients from 2004 to 2015 who were followed for at least 2 years after diagnosis; 610 had diabetes, a known risk factor for osteomyelitis and amputation, and 576 did not.
Comorbidities were considerably more common in the diabetes group, including PVD and heart failure, but also chronic obstructive pulmonary disease, previous heart attack, prior amputation, and especially renal disease. The 2-year amputation incidence was also higher in the diabetes group (43.1% vs. 12.3%), as was 2-year mortality (22.3% vs. 15.5%).
Odds ratios for lower limb amputation climbed in a stepwise fashion on multivariate analysis, from almost a 100% increase in men and in black patients to a 158% increase among patients with past amputations; a 206% increase with PVD; a 256% increase in patients with type 2 diabetes, and a 349% increase among patients with type 1 diabetes. The investigators were puzzled that the amputation risk was higher among type 1 patients than in those with type 2, because comorbidity burdens are generally higher in type 2 diabetes.
No data was provided on treatment differences between the groups, including antibiotic use.
The work was funded by the National Institutes of Health. The investigators reported no relevant disclosures.
SOURCE: Keeney-Bonthrone T et al. J Am Coll Surg. 2018 Oct;227(4), S105.
BOSTON – The higher the comorbidity burden, the greater the likelihood that osteomyelitis will lead to amputation within 2 years, according to a review of 1,186 adult osteomyelitis patients at the University of Michigan, Ann Arbor.
The limb amputation incidence was 7.2% over 2 years in patients with no comorbidities, 21.4% among patients with heart failure, 36.1% in patients with diabetes, and 36.7% among those with peripheral vascular disease (PVD).
The 2-year incidence marched steadily upward with combined comorbidities to 47.4% in patients with diabetes and heart failure; 64.5% in patients with diabetes and PVD; and 75.0% in patients with diabetes, heart failure, and PVD.
“What this means is that looking at diabetes versus no diabetes alone is not sufficient to gauge the risk of amputation. We have to look at the patient’s comorbidity profile as a whole; greater comorbidity burden and different combinations of comorbidities [increase] amputation incidence, but there’s considerable risk [7.2%] even among otherwise healthy patients,” said lead investigator Toby Keeney-Bonthrone, a medical student at the university.
The ultimate goal of the work is to develop an osteomyelitis amputation risk calculator for physicians and patients to improve decision making, validated by nationwide data. “The question is if some patients would benefit from [an earlier,] more prophylactic amputation. Would it be better to just take off the limb and be done with it, and would that decrease overall morbidity?” he said at the annual clinical congress of the American College of Surgeons.
“We often find ourselves reacting to osteomyelitis as it progresses. I think patients deserve a better deal than that. They deserve for us to think one or two steps ahead,” Mr. Keeney-Bonthrone said.
The immediate goal of the study was to fill the data gap on long-term osteomyelitis outcomes, something that hasn’t been addressed much in the literature. The team reviewed adult patients from 2004 to 2015 who were followed for at least 2 years after diagnosis; 610 had diabetes, a known risk factor for osteomyelitis and amputation, and 576 did not.
Comorbidities were considerably more common in the diabetes group, including PVD and heart failure, but also chronic obstructive pulmonary disease, previous heart attack, prior amputation, and especially renal disease. The 2-year amputation incidence was also higher in the diabetes group (43.1% vs. 12.3%), as was 2-year mortality (22.3% vs. 15.5%).
Odds ratios for lower limb amputation climbed in a stepwise fashion on multivariate analysis, from almost a 100% increase in men and in black patients to a 158% increase among patients with past amputations; a 206% increase with PVD; a 256% increase in patients with type 2 diabetes, and a 349% increase among patients with type 1 diabetes. The investigators were puzzled that the amputation risk was higher among type 1 patients than in those with type 2, because comorbidity burdens are generally higher in type 2 diabetes.
No data was provided on treatment differences between the groups, including antibiotic use.
The work was funded by the National Institutes of Health. The investigators reported no relevant disclosures.
SOURCE: Keeney-Bonthrone T et al. J Am Coll Surg. 2018 Oct;227(4), S105.
BOSTON – The higher the comorbidity burden, the greater the likelihood that osteomyelitis will lead to amputation within 2 years, according to a review of 1,186 adult osteomyelitis patients at the University of Michigan, Ann Arbor.
The limb amputation incidence was 7.2% over 2 years in patients with no comorbidities, 21.4% among patients with heart failure, 36.1% in patients with diabetes, and 36.7% among those with peripheral vascular disease (PVD).
The 2-year incidence marched steadily upward with combined comorbidities to 47.4% in patients with diabetes and heart failure; 64.5% in patients with diabetes and PVD; and 75.0% in patients with diabetes, heart failure, and PVD.
“What this means is that looking at diabetes versus no diabetes alone is not sufficient to gauge the risk of amputation. We have to look at the patient’s comorbidity profile as a whole; greater comorbidity burden and different combinations of comorbidities [increase] amputation incidence, but there’s considerable risk [7.2%] even among otherwise healthy patients,” said lead investigator Toby Keeney-Bonthrone, a medical student at the university.
The ultimate goal of the work is to develop an osteomyelitis amputation risk calculator for physicians and patients to improve decision making, validated by nationwide data. “The question is if some patients would benefit from [an earlier,] more prophylactic amputation. Would it be better to just take off the limb and be done with it, and would that decrease overall morbidity?” he said at the annual clinical congress of the American College of Surgeons.
“We often find ourselves reacting to osteomyelitis as it progresses. I think patients deserve a better deal than that. They deserve for us to think one or two steps ahead,” Mr. Keeney-Bonthrone said.
The immediate goal of the study was to fill the data gap on long-term osteomyelitis outcomes, something that hasn’t been addressed much in the literature. The team reviewed adult patients from 2004 to 2015 who were followed for at least 2 years after diagnosis; 610 had diabetes, a known risk factor for osteomyelitis and amputation, and 576 did not.
Comorbidities were considerably more common in the diabetes group, including PVD and heart failure, but also chronic obstructive pulmonary disease, previous heart attack, prior amputation, and especially renal disease. The 2-year amputation incidence was also higher in the diabetes group (43.1% vs. 12.3%), as was 2-year mortality (22.3% vs. 15.5%).
Odds ratios for lower limb amputation climbed in a stepwise fashion on multivariate analysis, from almost a 100% increase in men and in black patients to a 158% increase among patients with past amputations; a 206% increase with PVD; a 256% increase in patients with type 2 diabetes, and a 349% increase among patients with type 1 diabetes. The investigators were puzzled that the amputation risk was higher among type 1 patients than in those with type 2, because comorbidity burdens are generally higher in type 2 diabetes.
No data was provided on treatment differences between the groups, including antibiotic use.
The work was funded by the National Institutes of Health. The investigators reported no relevant disclosures.
SOURCE: Keeney-Bonthrone T et al. J Am Coll Surg. 2018 Oct;227(4), S105.
REPORTING FROM THE 2018 ACS CLINICAL CONGRESS
Key clinical point:
Major finding: The 2-year incidence marched steadily upward with combined comorbidities to 47.5% in patients with diabetes and heart failure; 64.5% in patients with diabetes and peripheral vascular disease, and 75% in patients with diabetes, heart failure, and peripheral vascular disease.
Study details: A review of 1,186 adult osteomyelitis patients
Disclosures: The work was funded by the National Institutes of Health. The investigators reported no relevant disclosures.
Source: Keeney-Bonthrone T et al. J Am Coll Surg. 2018 Oct;227(4), S105.