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Two novel approaches for infected ventral hernia mesh
BOSTON – Deep according to Cleveland Clinic investigators.
When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.
The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.
The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
Almost 80% salvageable
Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.
They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm2, “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.
Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.
Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.
In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.
A hybrid approach
When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.
The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.
The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.
Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m2. Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm2. Patients spent an average of 11 days in the hospital.
During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.
“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.
Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
BOSTON – Deep according to Cleveland Clinic investigators.
When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.
The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.
The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
Almost 80% salvageable
Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.
They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm2, “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.
Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.
Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.
In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.
A hybrid approach
When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.
The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.
The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.
Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m2. Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm2. Patients spent an average of 11 days in the hospital.
During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.
“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.
Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
BOSTON – Deep according to Cleveland Clinic investigators.
When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.
The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.
The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
Almost 80% salvageable
Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.
They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm2, “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.
Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.
Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.
In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.
A hybrid approach
When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.
The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.
The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.
Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m2. Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm2. Patients spent an average of 11 days in the hospital.
During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.
“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.
Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
REPORTING FROM THE ACS CLINICAL CONGRESS
Key clinical point: Infected mesh can sometimes be left in place, and a new surgical approach splits the difference between immediate and staged reconstruction.
Major finding: The salvage rate for infected ventral hernia mesh was almost 80% at 8 months, and the recurrence rate was 11.3% with hybrid reconstruction at 9 months.
Study details: Reviews of 24 infected mesh cases and 53 hybrid repairs
Disclosures: The study leads didn’t have any disclosures, and there was no external funding.
Discussing immunization with vaccine-hesitant parents requires caring, individualized approach
ORLANDO – Putting parents at ease, making vaccination the default option during discussions, appealing to their identity as a good parent, and focusing on positive word choice during discussions are the techniques two pediatricians have recommended using to get vaccine-hesitant parents to immunize their children.
“Your goal is to get parents to immunize their kids,” Katrina Saba, MD, of the Permanente Medical Group in Oakland, Calif., said during an interactive group panel at the annual meeting of the American Academy of Pediatrics. “Our goal is not to win a debate. You don’t have to correct every mistaken idea.”
“And really importantly, as we know, belief trumps science,” she added. “Their belief is so much stronger than our proof, and their belief will not be changed by evidence.”
Many parents who are vaccine- hesitant also belong to a social network that forms or reinforces their beliefs, and attacking those beliefs is the same as attacking their identity, Dr. Saba noted. “When you attack someone’s identity, you are immediately seen as not like them, and if you’re not like them, you’ve lost your strength in persuading them.”
Dr. Saba; Kenneth Hempstead, MD; and other pediatricians and educators in the Permanente Medical Group developed a framework for pediatricians and educators to talk with their patients about immunization at their center after California passed a law in 2013 that required health care professionals to discuss vaccines with patients and sign off that they had that discussion.
“We felt that, if we were going to be by law required to have that discussion, maybe we needed some new tools to have [the discussion] more effectively,” Dr. Saba said. “Because clearly, [what we were doing ] wasn’t working or there wouldn’t have been a need for that law.”
Dr. Hempstead explained the concerns of three major categories of vaccine-hesitant parents: those patients who are unsure of whether they should vaccinate, parents who wish to delay vaccination, and parents who refuse vaccination of their children.
Each parent requires a different approach for discussing the importance of vaccination based on their level of vaccine hesitancy, he said. For parents who are unsure, they may require general information about the safety and importance of vaccines.
Parents who delay immunization may have less trust in vaccines, have done research in their own social networks, and may present alternatives to a standard immunization schedule or want to omit certain vaccines from their child’s immunization schedule, he noted. Using the analogy of a car seat is one approach to identify the importance of vaccination to these parents: “Waiting to give the shots is like putting your baby in the car seat after you’ve already arrived at the store – the protection isn’t there for the most important part of the journey!”
In cases where parents refuse vaccination, you should not expect to change a parent’s mind in a single visit, but instead focus on building the patient-provider bond. However, presenting information the parent may have already seen, such as vaccination data from the Food and Drug Administration or Centers for Disease Control and Prevention, may alienate parents who identify with groups that share vaccine-hesitant viewpoints and erode your ability to persuade a parent’s intent to vaccinate.
A study by Nyhan et al. randomized parents to receive one of four pieces of interventions about the MMR vaccine: information from the CDC explaining the lack of evidence linking autism and the vaccine, information about the dangers of the diseases prevented by the vaccine, images of children who have had diseases prevented by the vaccine, and a “dramatic narrative” from a CDC fact sheet about a child who nearly died of measles. The researchers found no informational intervention helped in persuading to vaccinate in parents who had the “least favorable” attitudes toward the vaccine. And in the case of the dramatic narrative, there was an increased misperception about the MMR vaccine (Pediatrics. 2014;133[4]:e835-e842).
Dr. Hempstead and Dr. Saba outlined four rhetorical devices to include in conversations with patients about vaccination: cognitive ease, natural assumption, appeal to identity, and using advantageous terms.
Cognitive ease
Cognitive ease means creating an environment in which the patient is relaxed, comfortable, and more likely to be agreeable. Recognize when the tone shifts, and strive to maintain this calm and comfortable environment throughout the discussion. “If your blood pressure is coming up, that means theirs is, too,” Dr. Hempstead said.
Natural assumption
How you are offering the vaccination also matters, he added. Rather than asking whether a patient wants to vaccinate (“Have you thought about your flu vaccine this year?”), instead frame the discussion with vaccination as the default option (“Is your child due for a flu vaccination this year? Yes, he is. Let’s get that taken care of today”). Equating inaction with vaccination prevents the risk fallacy phenomenon from occurring in which, when given multiple options, people give equal weight to each option and may choose not to vaccinate, Dr. Hempstead noted.
Dr. Saba cited research that backed this approach. In a study by Opel et al., using a “presumptive” approach instead of a “participatory” approach when discussing a provider’s recommendation to vaccinate helped: The presumptive conversations had an odds ratio of 17.5, compared with the participatory approach. In cases in which parents resisted the provider’s recommendations, 50% of providers persisted with their original recommendations, and 47% of parents who initially resisted the recommendations agreed to vaccinate (Pediatrics. 2013;132[6]:1037-46).
Appeal to identity
Another strategy to use is appealing to the patient’s identity as a good parent and link the concept of vaccination with the good parent identity. Forging a new common identity with the parents through common beliefs – such as recognizing that networks to which parents belong are an important part of his or her identify – and reemphasizing the mutual desire to protect the child is another strategy.
Using advantageous terms
Positive terms, such as “protection,” “health,” “safety,” and “what’s best,” are much better words to use in conversation with parents and have more staying power than negative terms, like “autism” and “side effects,” Dr. Hempstead said.
“Stay with positive messaging,” he said. “Immediately coming back to the positive impact of this vaccine, why we care so much, why we’re doing this vaccine, is absolutely critical.”
Dr. Hempstead and Dr. Saba reported no relevant conflicts of interest.
ORLANDO – Putting parents at ease, making vaccination the default option during discussions, appealing to their identity as a good parent, and focusing on positive word choice during discussions are the techniques two pediatricians have recommended using to get vaccine-hesitant parents to immunize their children.
“Your goal is to get parents to immunize their kids,” Katrina Saba, MD, of the Permanente Medical Group in Oakland, Calif., said during an interactive group panel at the annual meeting of the American Academy of Pediatrics. “Our goal is not to win a debate. You don’t have to correct every mistaken idea.”
“And really importantly, as we know, belief trumps science,” she added. “Their belief is so much stronger than our proof, and their belief will not be changed by evidence.”
Many parents who are vaccine- hesitant also belong to a social network that forms or reinforces their beliefs, and attacking those beliefs is the same as attacking their identity, Dr. Saba noted. “When you attack someone’s identity, you are immediately seen as not like them, and if you’re not like them, you’ve lost your strength in persuading them.”
Dr. Saba; Kenneth Hempstead, MD; and other pediatricians and educators in the Permanente Medical Group developed a framework for pediatricians and educators to talk with their patients about immunization at their center after California passed a law in 2013 that required health care professionals to discuss vaccines with patients and sign off that they had that discussion.
“We felt that, if we were going to be by law required to have that discussion, maybe we needed some new tools to have [the discussion] more effectively,” Dr. Saba said. “Because clearly, [what we were doing ] wasn’t working or there wouldn’t have been a need for that law.”
Dr. Hempstead explained the concerns of three major categories of vaccine-hesitant parents: those patients who are unsure of whether they should vaccinate, parents who wish to delay vaccination, and parents who refuse vaccination of their children.
Each parent requires a different approach for discussing the importance of vaccination based on their level of vaccine hesitancy, he said. For parents who are unsure, they may require general information about the safety and importance of vaccines.
Parents who delay immunization may have less trust in vaccines, have done research in their own social networks, and may present alternatives to a standard immunization schedule or want to omit certain vaccines from their child’s immunization schedule, he noted. Using the analogy of a car seat is one approach to identify the importance of vaccination to these parents: “Waiting to give the shots is like putting your baby in the car seat after you’ve already arrived at the store – the protection isn’t there for the most important part of the journey!”
In cases where parents refuse vaccination, you should not expect to change a parent’s mind in a single visit, but instead focus on building the patient-provider bond. However, presenting information the parent may have already seen, such as vaccination data from the Food and Drug Administration or Centers for Disease Control and Prevention, may alienate parents who identify with groups that share vaccine-hesitant viewpoints and erode your ability to persuade a parent’s intent to vaccinate.
A study by Nyhan et al. randomized parents to receive one of four pieces of interventions about the MMR vaccine: information from the CDC explaining the lack of evidence linking autism and the vaccine, information about the dangers of the diseases prevented by the vaccine, images of children who have had diseases prevented by the vaccine, and a “dramatic narrative” from a CDC fact sheet about a child who nearly died of measles. The researchers found no informational intervention helped in persuading to vaccinate in parents who had the “least favorable” attitudes toward the vaccine. And in the case of the dramatic narrative, there was an increased misperception about the MMR vaccine (Pediatrics. 2014;133[4]:e835-e842).
Dr. Hempstead and Dr. Saba outlined four rhetorical devices to include in conversations with patients about vaccination: cognitive ease, natural assumption, appeal to identity, and using advantageous terms.
Cognitive ease
Cognitive ease means creating an environment in which the patient is relaxed, comfortable, and more likely to be agreeable. Recognize when the tone shifts, and strive to maintain this calm and comfortable environment throughout the discussion. “If your blood pressure is coming up, that means theirs is, too,” Dr. Hempstead said.
Natural assumption
How you are offering the vaccination also matters, he added. Rather than asking whether a patient wants to vaccinate (“Have you thought about your flu vaccine this year?”), instead frame the discussion with vaccination as the default option (“Is your child due for a flu vaccination this year? Yes, he is. Let’s get that taken care of today”). Equating inaction with vaccination prevents the risk fallacy phenomenon from occurring in which, when given multiple options, people give equal weight to each option and may choose not to vaccinate, Dr. Hempstead noted.
Dr. Saba cited research that backed this approach. In a study by Opel et al., using a “presumptive” approach instead of a “participatory” approach when discussing a provider’s recommendation to vaccinate helped: The presumptive conversations had an odds ratio of 17.5, compared with the participatory approach. In cases in which parents resisted the provider’s recommendations, 50% of providers persisted with their original recommendations, and 47% of parents who initially resisted the recommendations agreed to vaccinate (Pediatrics. 2013;132[6]:1037-46).
Appeal to identity
Another strategy to use is appealing to the patient’s identity as a good parent and link the concept of vaccination with the good parent identity. Forging a new common identity with the parents through common beliefs – such as recognizing that networks to which parents belong are an important part of his or her identify – and reemphasizing the mutual desire to protect the child is another strategy.
Using advantageous terms
Positive terms, such as “protection,” “health,” “safety,” and “what’s best,” are much better words to use in conversation with parents and have more staying power than negative terms, like “autism” and “side effects,” Dr. Hempstead said.
“Stay with positive messaging,” he said. “Immediately coming back to the positive impact of this vaccine, why we care so much, why we’re doing this vaccine, is absolutely critical.”
Dr. Hempstead and Dr. Saba reported no relevant conflicts of interest.
ORLANDO – Putting parents at ease, making vaccination the default option during discussions, appealing to their identity as a good parent, and focusing on positive word choice during discussions are the techniques two pediatricians have recommended using to get vaccine-hesitant parents to immunize their children.
“Your goal is to get parents to immunize their kids,” Katrina Saba, MD, of the Permanente Medical Group in Oakland, Calif., said during an interactive group panel at the annual meeting of the American Academy of Pediatrics. “Our goal is not to win a debate. You don’t have to correct every mistaken idea.”
“And really importantly, as we know, belief trumps science,” she added. “Their belief is so much stronger than our proof, and their belief will not be changed by evidence.”
Many parents who are vaccine- hesitant also belong to a social network that forms or reinforces their beliefs, and attacking those beliefs is the same as attacking their identity, Dr. Saba noted. “When you attack someone’s identity, you are immediately seen as not like them, and if you’re not like them, you’ve lost your strength in persuading them.”
Dr. Saba; Kenneth Hempstead, MD; and other pediatricians and educators in the Permanente Medical Group developed a framework for pediatricians and educators to talk with their patients about immunization at their center after California passed a law in 2013 that required health care professionals to discuss vaccines with patients and sign off that they had that discussion.
“We felt that, if we were going to be by law required to have that discussion, maybe we needed some new tools to have [the discussion] more effectively,” Dr. Saba said. “Because clearly, [what we were doing ] wasn’t working or there wouldn’t have been a need for that law.”
Dr. Hempstead explained the concerns of three major categories of vaccine-hesitant parents: those patients who are unsure of whether they should vaccinate, parents who wish to delay vaccination, and parents who refuse vaccination of their children.
Each parent requires a different approach for discussing the importance of vaccination based on their level of vaccine hesitancy, he said. For parents who are unsure, they may require general information about the safety and importance of vaccines.
Parents who delay immunization may have less trust in vaccines, have done research in their own social networks, and may present alternatives to a standard immunization schedule or want to omit certain vaccines from their child’s immunization schedule, he noted. Using the analogy of a car seat is one approach to identify the importance of vaccination to these parents: “Waiting to give the shots is like putting your baby in the car seat after you’ve already arrived at the store – the protection isn’t there for the most important part of the journey!”
In cases where parents refuse vaccination, you should not expect to change a parent’s mind in a single visit, but instead focus on building the patient-provider bond. However, presenting information the parent may have already seen, such as vaccination data from the Food and Drug Administration or Centers for Disease Control and Prevention, may alienate parents who identify with groups that share vaccine-hesitant viewpoints and erode your ability to persuade a parent’s intent to vaccinate.
A study by Nyhan et al. randomized parents to receive one of four pieces of interventions about the MMR vaccine: information from the CDC explaining the lack of evidence linking autism and the vaccine, information about the dangers of the diseases prevented by the vaccine, images of children who have had diseases prevented by the vaccine, and a “dramatic narrative” from a CDC fact sheet about a child who nearly died of measles. The researchers found no informational intervention helped in persuading to vaccinate in parents who had the “least favorable” attitudes toward the vaccine. And in the case of the dramatic narrative, there was an increased misperception about the MMR vaccine (Pediatrics. 2014;133[4]:e835-e842).
Dr. Hempstead and Dr. Saba outlined four rhetorical devices to include in conversations with patients about vaccination: cognitive ease, natural assumption, appeal to identity, and using advantageous terms.
Cognitive ease
Cognitive ease means creating an environment in which the patient is relaxed, comfortable, and more likely to be agreeable. Recognize when the tone shifts, and strive to maintain this calm and comfortable environment throughout the discussion. “If your blood pressure is coming up, that means theirs is, too,” Dr. Hempstead said.
Natural assumption
How you are offering the vaccination also matters, he added. Rather than asking whether a patient wants to vaccinate (“Have you thought about your flu vaccine this year?”), instead frame the discussion with vaccination as the default option (“Is your child due for a flu vaccination this year? Yes, he is. Let’s get that taken care of today”). Equating inaction with vaccination prevents the risk fallacy phenomenon from occurring in which, when given multiple options, people give equal weight to each option and may choose not to vaccinate, Dr. Hempstead noted.
Dr. Saba cited research that backed this approach. In a study by Opel et al., using a “presumptive” approach instead of a “participatory” approach when discussing a provider’s recommendation to vaccinate helped: The presumptive conversations had an odds ratio of 17.5, compared with the participatory approach. In cases in which parents resisted the provider’s recommendations, 50% of providers persisted with their original recommendations, and 47% of parents who initially resisted the recommendations agreed to vaccinate (Pediatrics. 2013;132[6]:1037-46).
Appeal to identity
Another strategy to use is appealing to the patient’s identity as a good parent and link the concept of vaccination with the good parent identity. Forging a new common identity with the parents through common beliefs – such as recognizing that networks to which parents belong are an important part of his or her identify – and reemphasizing the mutual desire to protect the child is another strategy.
Using advantageous terms
Positive terms, such as “protection,” “health,” “safety,” and “what’s best,” are much better words to use in conversation with parents and have more staying power than negative terms, like “autism” and “side effects,” Dr. Hempstead said.
“Stay with positive messaging,” he said. “Immediately coming back to the positive impact of this vaccine, why we care so much, why we’re doing this vaccine, is absolutely critical.”
Dr. Hempstead and Dr. Saba reported no relevant conflicts of interest.
EXPERT ANALYSIS FROM AAP 18
Circulating tumor DNA identified by fragment size
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: The size of cell-free DNA could be used to single out circulating tumor DNA.
Major finding: Circulating tumor DNA fragments are more commonly found in the 90-150 base pair range.
Study details: A study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls.
Disclosures: The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in circulating tumor DNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
Source: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Innovations in Dermatology: Sarecycline Approved for Acne
Novel theory explains SSRIs’ variable efficacy
BARCELONA – New evidence from the landmark 12-year-old STAR*D clinical trial provides fresh support for a novel Italian hypothesis that the efficacy of selective serotonin reuptake inhibitors in major depressive disorder results from their capacity to amplify the influence of living conditions upon mood.
“This hypothesis claims that SSRIs do not affect mood by themselves, but by increasing brain plasticity to render an individual more susceptible to the influence of living conditions. So in a positive environment, treatment leads to a beneficial outcome, and in a stressful environment it may lead to a worse prognosis,” Aurelia Viglione explained at the annual congress of the European College of Neuropsychopharmacology.
This originally was demonstrated by her senior coinvestigators in mouse studies, which showed increased brain plasticity and responsiveness of mood to living conditions in the presence of the serotonin boost provided by SSRIs. Now this animal research has been confirmed in a more clinically relevant fashion via a secondary analysis of the venerable National Institute of Mental Health–funded STAR*D (Sequenced Treatment Alternatives to Relieve Depression) data set, which Ms. Viglione presented at the ECNP congress.
This hypothesis, which she and her colleagues have dubbed the “undirected susceptibility to change” hypothesis of the mechanism of action of SSRIs, attempts to account for the drugs’ highly variable efficacy. As prescribing physicians and their often-frustrated patients with major depression are all too aware, the SSRIs – the most widely prescribed treatment for the disorder – induce remission in only 30%-40% of patients, while an additional 30%-40% fail to experience even a significant response. And despite much research effort, to date there is no reliable way to match the best antidepressant to a given individual in accord with the current priority to develop a personalized medicine approach.
The undirected susceptibility to change hypothesis provides a plausible explanation for these mixed clinical outcomes. The hypothesis posits that high serotonin levels lead to increased brain plasticity and consequent openness to change in mood, which can be for the better or worse – depending upon the quality of the surrounding environment.
Ms. Viglione, a PhD student in neuroscience at the University of Pisa (Italy), presented a study of a 591-patient subset of patients with major depression in STAR*D who received citalopram at 20 mg/day for 4 weeks, at which point the 40% of participants who weren’t showing a sufficiently favorable response trend had their citalopram increased to 40 mg/day. Patients’ living conditions were categorized as favorable or adverse based upon an amalgam of sociodemographic characteristics, including employment status, education, marital status, income, insurance status, ethnicity, drug abuse, and history of traumatic events. Treatment response was measured using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) score.
. Patients were more likely to achieve remission as defined by a QIDS-SR16 score of 5 or less at week 6 if they had a college education, a job, higher income, and/or private health insurance than if those proxies for favorable living conditions were not present.
The impact of sociodemographic factors on change in mood was much larger in patients on citalopram at 40 mg/day than 20 mg/day. For example, having a college education rather than a high school education was independently associated with up to a 37-fold greater remission rate among patients on the higher dose of the SSRI, depending upon their sociodemographic status, compared with a 2-fold greater likelihood of remission in patients on citalopram at 20 mg/day.
“The correlation is very high. It’s a very huge effect,” Ms. Viglione commented.
On the other hand, the 40-mg dose also was associated with an increased likelihood of worsening in patients living in an unfavorable environment. For example, 35% of patients in the 40-mg group with only a high school degree showed worsening depression, compared with 21% on citalopram at 20 mg/day. And 40% of low-income patients on citalopram at 40 mg/day showed worsening depression, compared with 35% of low-income patients on 20 mg. These figures probably underestimate the true downside of higher-dose treatment in patients living in an adverse environment, because STAR*D guidelines called for treatment discontinuation in the setting of worsening depression, she noted.
The correlation between higher-dose SSRI therapy, sociodemographic environment, and change in depressive symptoms was not uniform across all symptom categories. Ms. Viglione and her colleagues grouped the elements of the QIDS-SR16 rating scale into three domains: core emotional symptoms, sleep/insomnia symptoms, and weight/appetite. They found that the impact of higher-dose therapy in combination with favorable living conditions was greatest on sleep/insomnia symptoms.
The next step for the Italian investigators will be to determine in a prospective study whether the undirected susceptibility to change hypothesis can predict which patients will benefit from SSRI therapy.
Ms. Viglione reported having no financial conflicts regarding her study, which was funded by the Italian Ministry of Health.
BARCELONA – New evidence from the landmark 12-year-old STAR*D clinical trial provides fresh support for a novel Italian hypothesis that the efficacy of selective serotonin reuptake inhibitors in major depressive disorder results from their capacity to amplify the influence of living conditions upon mood.
“This hypothesis claims that SSRIs do not affect mood by themselves, but by increasing brain plasticity to render an individual more susceptible to the influence of living conditions. So in a positive environment, treatment leads to a beneficial outcome, and in a stressful environment it may lead to a worse prognosis,” Aurelia Viglione explained at the annual congress of the European College of Neuropsychopharmacology.
This originally was demonstrated by her senior coinvestigators in mouse studies, which showed increased brain plasticity and responsiveness of mood to living conditions in the presence of the serotonin boost provided by SSRIs. Now this animal research has been confirmed in a more clinically relevant fashion via a secondary analysis of the venerable National Institute of Mental Health–funded STAR*D (Sequenced Treatment Alternatives to Relieve Depression) data set, which Ms. Viglione presented at the ECNP congress.
This hypothesis, which she and her colleagues have dubbed the “undirected susceptibility to change” hypothesis of the mechanism of action of SSRIs, attempts to account for the drugs’ highly variable efficacy. As prescribing physicians and their often-frustrated patients with major depression are all too aware, the SSRIs – the most widely prescribed treatment for the disorder – induce remission in only 30%-40% of patients, while an additional 30%-40% fail to experience even a significant response. And despite much research effort, to date there is no reliable way to match the best antidepressant to a given individual in accord with the current priority to develop a personalized medicine approach.
The undirected susceptibility to change hypothesis provides a plausible explanation for these mixed clinical outcomes. The hypothesis posits that high serotonin levels lead to increased brain plasticity and consequent openness to change in mood, which can be for the better or worse – depending upon the quality of the surrounding environment.
Ms. Viglione, a PhD student in neuroscience at the University of Pisa (Italy), presented a study of a 591-patient subset of patients with major depression in STAR*D who received citalopram at 20 mg/day for 4 weeks, at which point the 40% of participants who weren’t showing a sufficiently favorable response trend had their citalopram increased to 40 mg/day. Patients’ living conditions were categorized as favorable or adverse based upon an amalgam of sociodemographic characteristics, including employment status, education, marital status, income, insurance status, ethnicity, drug abuse, and history of traumatic events. Treatment response was measured using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) score.
. Patients were more likely to achieve remission as defined by a QIDS-SR16 score of 5 or less at week 6 if they had a college education, a job, higher income, and/or private health insurance than if those proxies for favorable living conditions were not present.
The impact of sociodemographic factors on change in mood was much larger in patients on citalopram at 40 mg/day than 20 mg/day. For example, having a college education rather than a high school education was independently associated with up to a 37-fold greater remission rate among patients on the higher dose of the SSRI, depending upon their sociodemographic status, compared with a 2-fold greater likelihood of remission in patients on citalopram at 20 mg/day.
“The correlation is very high. It’s a very huge effect,” Ms. Viglione commented.
On the other hand, the 40-mg dose also was associated with an increased likelihood of worsening in patients living in an unfavorable environment. For example, 35% of patients in the 40-mg group with only a high school degree showed worsening depression, compared with 21% on citalopram at 20 mg/day. And 40% of low-income patients on citalopram at 40 mg/day showed worsening depression, compared with 35% of low-income patients on 20 mg. These figures probably underestimate the true downside of higher-dose treatment in patients living in an adverse environment, because STAR*D guidelines called for treatment discontinuation in the setting of worsening depression, she noted.
The correlation between higher-dose SSRI therapy, sociodemographic environment, and change in depressive symptoms was not uniform across all symptom categories. Ms. Viglione and her colleagues grouped the elements of the QIDS-SR16 rating scale into three domains: core emotional symptoms, sleep/insomnia symptoms, and weight/appetite. They found that the impact of higher-dose therapy in combination with favorable living conditions was greatest on sleep/insomnia symptoms.
The next step for the Italian investigators will be to determine in a prospective study whether the undirected susceptibility to change hypothesis can predict which patients will benefit from SSRI therapy.
Ms. Viglione reported having no financial conflicts regarding her study, which was funded by the Italian Ministry of Health.
BARCELONA – New evidence from the landmark 12-year-old STAR*D clinical trial provides fresh support for a novel Italian hypothesis that the efficacy of selective serotonin reuptake inhibitors in major depressive disorder results from their capacity to amplify the influence of living conditions upon mood.
“This hypothesis claims that SSRIs do not affect mood by themselves, but by increasing brain plasticity to render an individual more susceptible to the influence of living conditions. So in a positive environment, treatment leads to a beneficial outcome, and in a stressful environment it may lead to a worse prognosis,” Aurelia Viglione explained at the annual congress of the European College of Neuropsychopharmacology.
This originally was demonstrated by her senior coinvestigators in mouse studies, which showed increased brain plasticity and responsiveness of mood to living conditions in the presence of the serotonin boost provided by SSRIs. Now this animal research has been confirmed in a more clinically relevant fashion via a secondary analysis of the venerable National Institute of Mental Health–funded STAR*D (Sequenced Treatment Alternatives to Relieve Depression) data set, which Ms. Viglione presented at the ECNP congress.
This hypothesis, which she and her colleagues have dubbed the “undirected susceptibility to change” hypothesis of the mechanism of action of SSRIs, attempts to account for the drugs’ highly variable efficacy. As prescribing physicians and their often-frustrated patients with major depression are all too aware, the SSRIs – the most widely prescribed treatment for the disorder – induce remission in only 30%-40% of patients, while an additional 30%-40% fail to experience even a significant response. And despite much research effort, to date there is no reliable way to match the best antidepressant to a given individual in accord with the current priority to develop a personalized medicine approach.
The undirected susceptibility to change hypothesis provides a plausible explanation for these mixed clinical outcomes. The hypothesis posits that high serotonin levels lead to increased brain plasticity and consequent openness to change in mood, which can be for the better or worse – depending upon the quality of the surrounding environment.
Ms. Viglione, a PhD student in neuroscience at the University of Pisa (Italy), presented a study of a 591-patient subset of patients with major depression in STAR*D who received citalopram at 20 mg/day for 4 weeks, at which point the 40% of participants who weren’t showing a sufficiently favorable response trend had their citalopram increased to 40 mg/day. Patients’ living conditions were categorized as favorable or adverse based upon an amalgam of sociodemographic characteristics, including employment status, education, marital status, income, insurance status, ethnicity, drug abuse, and history of traumatic events. Treatment response was measured using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) score.
. Patients were more likely to achieve remission as defined by a QIDS-SR16 score of 5 or less at week 6 if they had a college education, a job, higher income, and/or private health insurance than if those proxies for favorable living conditions were not present.
The impact of sociodemographic factors on change in mood was much larger in patients on citalopram at 40 mg/day than 20 mg/day. For example, having a college education rather than a high school education was independently associated with up to a 37-fold greater remission rate among patients on the higher dose of the SSRI, depending upon their sociodemographic status, compared with a 2-fold greater likelihood of remission in patients on citalopram at 20 mg/day.
“The correlation is very high. It’s a very huge effect,” Ms. Viglione commented.
On the other hand, the 40-mg dose also was associated with an increased likelihood of worsening in patients living in an unfavorable environment. For example, 35% of patients in the 40-mg group with only a high school degree showed worsening depression, compared with 21% on citalopram at 20 mg/day. And 40% of low-income patients on citalopram at 40 mg/day showed worsening depression, compared with 35% of low-income patients on 20 mg. These figures probably underestimate the true downside of higher-dose treatment in patients living in an adverse environment, because STAR*D guidelines called for treatment discontinuation in the setting of worsening depression, she noted.
The correlation between higher-dose SSRI therapy, sociodemographic environment, and change in depressive symptoms was not uniform across all symptom categories. Ms. Viglione and her colleagues grouped the elements of the QIDS-SR16 rating scale into three domains: core emotional symptoms, sleep/insomnia symptoms, and weight/appetite. They found that the impact of higher-dose therapy in combination with favorable living conditions was greatest on sleep/insomnia symptoms.
The next step for the Italian investigators will be to determine in a prospective study whether the undirected susceptibility to change hypothesis can predict which patients will benefit from SSRI therapy.
Ms. Viglione reported having no financial conflicts regarding her study, which was funded by the Italian Ministry of Health.
REPORTING FROM THE ECNP CONGRESS
Key clinical point: There’s a new hypothesis to explain the mixed results of selective serotonin reuptake inhibitors for major depression.
Major finding: Improvement in symptoms of major depression was strongly correlated with SSRI dose and patients’ living conditions.
Study details: This secondary analysis of the STAR*D data set included 591 patients who received citalopram for major depression.
Disclosures: The presenter reported having no financial conflicts regarding the study, funded by the Italian Ministry of Health.
Draft JIA recommendations from ACR seek inactive disease
CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.
“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.
Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.
The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.
Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”
Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).
The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.
Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.
Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.
The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.
Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.
Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.
CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.
“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.
Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.
The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.
Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”
Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).
The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.
Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.
Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.
The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.
Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.
Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.
CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.
“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.
Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.
The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.
Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”
Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).
The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.
Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.
Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.
The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.
Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.
Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.
EXPERT ANALYSIS FROM THE ACR ANNUAL MEETING
Ob.Gyn. News welcomes Dr. Trolice to the board
Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.
He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.
Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.
Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.
He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.
Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.
Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.
He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.
Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.
Caffeinated coffee intake linked to lower rosacea risk
Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.
Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.
By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.
“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.
This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.
Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.
A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.
By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.
Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”
However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.
Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.
Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.
By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.
“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.
This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.
Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.
A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.
By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.
Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”
However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.
Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.
Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.
Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.
By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.
“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.
This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.
Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.
A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.
By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.
Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”
However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.
Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.
FROM JAMA DERMATOLOGY
Key clinical point: Caffeinated coffee intake was linked to decreased incidence of rosacea, while decaffeinated coffee and noncoffee sources of caffeine had no such effect.
Major finding: Consuming four or more servings of caffeinated coffee was associated with lower risk of rosacea versus one or fewer servings per month (hazard ratio, 0.77; P less than .001).
Study details: An analysis based on 82,737 participants in the Nurses’ Health Study II who responded to a question about rosacea.
Disclosures: Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from National Institutes of Health grants for the Nurses’ Health Study II and other sources.
Source: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.
Dulaglutide meets primary endpoint in REWIND
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Mood stabilizers protect bipolar patients from suicide
BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.
“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.
“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.
He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.
In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.
At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.
Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.
Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”
He reported having no financial conflicts regarding the study, funded by the Finnish government.
Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.
BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.
“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.
“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.
He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.
In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.
At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.
Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.
Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”
He reported having no financial conflicts regarding the study, funded by the Finnish government.
Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.
BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.
“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.
“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.
He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.
In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.
At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.
Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.
Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”
He reported having no financial conflicts regarding the study, funded by the Finnish government.
Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.
REPORTING FROM THE ECNP CONGRESS
Key clinical point: Lithium and valproic acid protect patients with bipolar disorder from suicide.
Major finding: The likelihood of suicide was reduced by two-thirds in bipolar patients on lithium, compared with that of patients not on the mood stabilizer.
Study details: This was a retrospective study of more than 18,000 Finnish patients hospitalized at some point for bipolar disorder and the medications they were on when a subset of them committed suicide.
Disclosures: The presenter reported having no financial conflicts regarding the study, funded by the Finnish government.