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Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.
International registry of laser surgery outcomes in the works
DENVER – Researchers in the early stages of from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.
“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”
A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.
For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.
Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).
The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.
The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”
The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.
[email protected]
DENVER – Researchers in the early stages of from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.
“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”
A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.
For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.
Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).
The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.
The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”
The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.
[email protected]
DENVER – Researchers in the early stages of from existing studies in the medical literature. They’ve also observed insufficient reporting of outcome definitions and under-representation of life impact domains.
“Today, laser therapy is not only an important treatment modality for cosmetic indications, but also for medical skin disorders and diseases,” lead study author Frederike Fransen said at the annual conference of the American Society for Laser Medicine and Surgery. “These disorders include inflammatory lesions, vascular and pigmented lesions, tumors, and scars. Although there are a lot of options for laser therapy, the evidence for most of these skin conditions is quite low, consisting mostly of case reports and case series. However, if we want more evidence-based practice, we need more practice-based evidence.”
A new effort to gain insight into safety and effectiveness of laser treatments known as the international Laser Treatment Dermatology Registry (LEAD) is a platform to address this challenge. “We envision a registry that connects expertise and experience of a large international team of laser specialists, clinicians, and researchers,” said Ms. Fransen, a PhD candidate in the department of dermatology at Amsterdam University Medical Center. “Our goal is to gain insight into safety and effectiveness of laser treatments.” The collaboration includes researchers from the Netherlands, Denmark, France, Germany, Italy, and Switzerland, and the team will be complemented by experts from the United States, Asia, and North Africa.
For the first phase of the endeavor, Ms. Fransen and Albert Wolkerstorfer, MD, PhD, of the University of Amsterdam worked with colleagues from the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) to develop a consensus of outcomes to be included in the registry. This involved a literature review of 350 articles to explore the outcomes used in laser research. From these, the researchers identified 100 articles for outcome mapping: 25 randomized, controlled trials, 44 trials that were not randomized or controlled, and 31 case reports. Their review yielded 98 outcomes and 53 outcome instruments.
Ultimately, outcomes were assigned to eight domains, Ms. Fransen said: appearance, long-term effects, physician-reported physical signs, patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning, and adverse events. Of these domains, the most commonly used in existing medical literature were appearance such as clinical improvement and clearance (81%), followed by adverse effects such as erythema and scarring (55%), physician-reported signs such as morphology (30%), and long-term effects such as recurrence (27%). Ms. Fransen and Dr. Wolkerstorfer observed under-representation of patient-centered outcomes, including satisfaction of appearance or treatment (29%), patient-reported physical signs such as overall state and severity of disease (12%), health-related quality of life (4%), and psychological functioning such as anxiety and depression (1%).
The analysis also revealed that different outcomes measures were used in the various studies, and inconstant definitions within scaling systems. For example, for clearance of lesions/no clearance of lesions, some studies defined excellent clearance as 75% or greater, and others defined marked clearance as 70% or greater. In addition, some studies that used percentage quintile grading as an outcome defined grade 5 as a greater than 95% improvement, while others defined grade 5 as “clear,” or a greater than 90% improvement.
The next step in developing the LEAD registry involves performing an international e-Delphi survey, a method to obtain agreement on outcomes for the registry among health care professionals and patients with different opinions and backgrounds. “The process ends when sufficient agreement is obtained,” Ms. Fransen said. “Looking at future steps, the development of this collaborative initiative with a minimum set of outcomes is essential. When establishing this registry we can achieve sufficient sample size and confirmatory cases toward stronger evidence of laser treatments for orphan diseases.”
The project was supported by the European Academy of Dermatology and Venereology and by an educational grant from ASLMS.
[email protected]
REPORTING FROM ASLMS 2019
How to cope with patients who get under your skin
DENVER – If you get the impression you’re dealing with more angry and manipulative patients than usual in the past several years, you’re not alone.
In 1999, as many as 15% of patient encounters were rated as difficult by health care providers, according to Tina S. Alster, MD (Arch Intern Med. 1999;159:1069-75). Today, upward of 30% of patient encounters are deemed difficult (Int J Res Med Sci. 2016;4[8]:3554-62). “That means one in three patients that you see have a problem that goes beyond the scope of our official training,” said Dr. Alster, who is the founding director of the Washington Institute of Dermatologic Laser Surgery and clinical professor of dermatology at Georgetown University, Washington. “If it was limited to a medical problem, we could handle it; that’s what we’re trained to do. The interpersonal issues and psychosocial implications of treatment are much more difficult.”
At the annual conference of the American Society for Laser Medicine and Surgery, Dr. Alster said that difficult patients put a strain on your practice and your relationship with them. “These patients put you on your heels. They often point out a problem that may or may not be related to something that you’re responsible for. It’s not usually because you are running late on the day of their visit and you make them late for something else. That situation is one you can prepare for, because you know you’re running late. It’s the other stuff you don’t realize that’s going on, which can cause problems.”
Setting limits
Being proactive can help lessen the ripple effect from patients who rock the boat. “You want to set limits with those patients before you even see them,” Dr. Alster said. “There are written contracts and policies that you should have in place. Since I perform mostly cosmetic procedures in my office, it is important that patients are made aware that payment is expected at the time of service and that my office does not bill nor accept insurance payments in order to prevent misunderstandings at check out.” She also declines requests to provide expert testimony for legal cases. “I’ve been in this business a long time, and every day I get requests to be an expert or to review a case involving a provider who may or may not have made a mistake. I really hate going down that rabbit hole.”
Another solution to keeping difficult patients in check is to collaborate with your entire office staff on how to best deal with them. “You need to present a united front with these patients: They’re going to divide and conquer, with complaints like, ‘How dare the doctor be so late. I’ve been waiting here for 30 minutes. Doesn’t she know I’m busy?’ ” Dr. Alster said. “You’re going to have to give them the tools to set limits as well. During our staff meetings, we review the upcoming patient schedule and identify potentially difficult situations in order to make sure the team is on the same page. Because my office is located in the power corridor of Washington [three blocks away from the White House] and my patient base is populated by prevalent personalities, expectations are extraordinarily high. As such, it is important that we set limits and rules that everyone can play by.”
Getting a sense of whether a patient is angry or manipulative can also help. An angry patient often holds an expectation that has been unmet, or harbors fears related to the treatment itself, she said, while a manipulative patient may engage in bullying, excessive flattery, or veiled threats. “They often expect specific treatments that have only worked for them in the past, even though it may be opposed to the treatment you recommend. They know better than you, even though you’re the expert.”
Communicating effectively with these two types of patients requires a slightly different approach. “With an angry patient, you want to share decision making,” Dr. Alster said. “Have them voice their concerns and come up with a plan together going forward. You’re not going to make that person less angry by telling them what to do.” The manipulative patient, meanwhile, requires a team approach. For example, she may ask your medical assistant for opinions on the treatment option you recommended during your office consultation with her, or second-guess your recommendation with that person altogether. “Everybody needs to know who the manipulative patients are and approach them as a team.”
The art of nonconfrontation
Dr. Alster brings a nonconfrontational approach to interactions with difficult patients. “You can apologize if you’ve kept them waiting, but you can’t apologize for everything all the time,” she said. “I may say something like, ‘I appreciate that your visit is running late. I apologize for the delay and want you to know that we take as much time as necessary for each patient and that unforeseen circumstances beyond our control sometimes arise.’ ” Another phrase she may use is, “I understand that this has been a stressful visit, but I want to talk to you about your experience and identify how we can improve subsequent appointments.”
Showing empathy never hurts. “Repeat back to them what you heard, and establish the fact that you understand,” Dr. Alster said. “Lower your voice, talk slowly, don’t get caught up in emotion. Otherwise, you’re going down in a sinkhole with them. Be wrong to be right. This encourages negotiation. You also want to document all patient interactions. Put every correspondence in the patient’s EMR.”
Dr. Alster advises clinicians to provide an outline of office policies and procedures to all patients, as well as written and verbal instructions related to their care. She also phones or emails patients undergoing a treatment for the first time. “Even if they’ve been in the practice for several years, if they received filler injections for the first time [instead of Botox], we still check in with those patients when they receive a first-time treatment to make sure they’re doing okay,” she said. “We’ll call them that evening or at the very least early the next morning to make sure that they don’t have any questions or concerns.”
If problems persist despite your best efforts, sometimes your best option is to dismiss difficult patients from your practice. “That’s only when everything else fails,” Dr. Alster said. “A concise termination letter should state a ‘breakdown in physician-patient relationship.’ I call it my ‘Dear John’ letter, and since 1990, I’ve only written six of these. A detailed explanation is usually not needed, but may be advisable depending on your state, to protect yourself from a liability standpoint. I instruct patients to contact the state medical society for referral to another provider and inform them that upon their written request, their medical records will be forwarded to their new provider. I also set up a reasonable timeline during which I will continue to see them for emergency visits to ensure that there is continuity of care, even when it is a cosmetic situation.”
Dr. Alster reported having no financial disclosures related to her presentation.
DENVER – If you get the impression you’re dealing with more angry and manipulative patients than usual in the past several years, you’re not alone.
In 1999, as many as 15% of patient encounters were rated as difficult by health care providers, according to Tina S. Alster, MD (Arch Intern Med. 1999;159:1069-75). Today, upward of 30% of patient encounters are deemed difficult (Int J Res Med Sci. 2016;4[8]:3554-62). “That means one in three patients that you see have a problem that goes beyond the scope of our official training,” said Dr. Alster, who is the founding director of the Washington Institute of Dermatologic Laser Surgery and clinical professor of dermatology at Georgetown University, Washington. “If it was limited to a medical problem, we could handle it; that’s what we’re trained to do. The interpersonal issues and psychosocial implications of treatment are much more difficult.”
At the annual conference of the American Society for Laser Medicine and Surgery, Dr. Alster said that difficult patients put a strain on your practice and your relationship with them. “These patients put you on your heels. They often point out a problem that may or may not be related to something that you’re responsible for. It’s not usually because you are running late on the day of their visit and you make them late for something else. That situation is one you can prepare for, because you know you’re running late. It’s the other stuff you don’t realize that’s going on, which can cause problems.”
Setting limits
Being proactive can help lessen the ripple effect from patients who rock the boat. “You want to set limits with those patients before you even see them,” Dr. Alster said. “There are written contracts and policies that you should have in place. Since I perform mostly cosmetic procedures in my office, it is important that patients are made aware that payment is expected at the time of service and that my office does not bill nor accept insurance payments in order to prevent misunderstandings at check out.” She also declines requests to provide expert testimony for legal cases. “I’ve been in this business a long time, and every day I get requests to be an expert or to review a case involving a provider who may or may not have made a mistake. I really hate going down that rabbit hole.”
Another solution to keeping difficult patients in check is to collaborate with your entire office staff on how to best deal with them. “You need to present a united front with these patients: They’re going to divide and conquer, with complaints like, ‘How dare the doctor be so late. I’ve been waiting here for 30 minutes. Doesn’t she know I’m busy?’ ” Dr. Alster said. “You’re going to have to give them the tools to set limits as well. During our staff meetings, we review the upcoming patient schedule and identify potentially difficult situations in order to make sure the team is on the same page. Because my office is located in the power corridor of Washington [three blocks away from the White House] and my patient base is populated by prevalent personalities, expectations are extraordinarily high. As such, it is important that we set limits and rules that everyone can play by.”
Getting a sense of whether a patient is angry or manipulative can also help. An angry patient often holds an expectation that has been unmet, or harbors fears related to the treatment itself, she said, while a manipulative patient may engage in bullying, excessive flattery, or veiled threats. “They often expect specific treatments that have only worked for them in the past, even though it may be opposed to the treatment you recommend. They know better than you, even though you’re the expert.”
Communicating effectively with these two types of patients requires a slightly different approach. “With an angry patient, you want to share decision making,” Dr. Alster said. “Have them voice their concerns and come up with a plan together going forward. You’re not going to make that person less angry by telling them what to do.” The manipulative patient, meanwhile, requires a team approach. For example, she may ask your medical assistant for opinions on the treatment option you recommended during your office consultation with her, or second-guess your recommendation with that person altogether. “Everybody needs to know who the manipulative patients are and approach them as a team.”
The art of nonconfrontation
Dr. Alster brings a nonconfrontational approach to interactions with difficult patients. “You can apologize if you’ve kept them waiting, but you can’t apologize for everything all the time,” she said. “I may say something like, ‘I appreciate that your visit is running late. I apologize for the delay and want you to know that we take as much time as necessary for each patient and that unforeseen circumstances beyond our control sometimes arise.’ ” Another phrase she may use is, “I understand that this has been a stressful visit, but I want to talk to you about your experience and identify how we can improve subsequent appointments.”
Showing empathy never hurts. “Repeat back to them what you heard, and establish the fact that you understand,” Dr. Alster said. “Lower your voice, talk slowly, don’t get caught up in emotion. Otherwise, you’re going down in a sinkhole with them. Be wrong to be right. This encourages negotiation. You also want to document all patient interactions. Put every correspondence in the patient’s EMR.”
Dr. Alster advises clinicians to provide an outline of office policies and procedures to all patients, as well as written and verbal instructions related to their care. She also phones or emails patients undergoing a treatment for the first time. “Even if they’ve been in the practice for several years, if they received filler injections for the first time [instead of Botox], we still check in with those patients when they receive a first-time treatment to make sure they’re doing okay,” she said. “We’ll call them that evening or at the very least early the next morning to make sure that they don’t have any questions or concerns.”
If problems persist despite your best efforts, sometimes your best option is to dismiss difficult patients from your practice. “That’s only when everything else fails,” Dr. Alster said. “A concise termination letter should state a ‘breakdown in physician-patient relationship.’ I call it my ‘Dear John’ letter, and since 1990, I’ve only written six of these. A detailed explanation is usually not needed, but may be advisable depending on your state, to protect yourself from a liability standpoint. I instruct patients to contact the state medical society for referral to another provider and inform them that upon their written request, their medical records will be forwarded to their new provider. I also set up a reasonable timeline during which I will continue to see them for emergency visits to ensure that there is continuity of care, even when it is a cosmetic situation.”
Dr. Alster reported having no financial disclosures related to her presentation.
DENVER – If you get the impression you’re dealing with more angry and manipulative patients than usual in the past several years, you’re not alone.
In 1999, as many as 15% of patient encounters were rated as difficult by health care providers, according to Tina S. Alster, MD (Arch Intern Med. 1999;159:1069-75). Today, upward of 30% of patient encounters are deemed difficult (Int J Res Med Sci. 2016;4[8]:3554-62). “That means one in three patients that you see have a problem that goes beyond the scope of our official training,” said Dr. Alster, who is the founding director of the Washington Institute of Dermatologic Laser Surgery and clinical professor of dermatology at Georgetown University, Washington. “If it was limited to a medical problem, we could handle it; that’s what we’re trained to do. The interpersonal issues and psychosocial implications of treatment are much more difficult.”
At the annual conference of the American Society for Laser Medicine and Surgery, Dr. Alster said that difficult patients put a strain on your practice and your relationship with them. “These patients put you on your heels. They often point out a problem that may or may not be related to something that you’re responsible for. It’s not usually because you are running late on the day of their visit and you make them late for something else. That situation is one you can prepare for, because you know you’re running late. It’s the other stuff you don’t realize that’s going on, which can cause problems.”
Setting limits
Being proactive can help lessen the ripple effect from patients who rock the boat. “You want to set limits with those patients before you even see them,” Dr. Alster said. “There are written contracts and policies that you should have in place. Since I perform mostly cosmetic procedures in my office, it is important that patients are made aware that payment is expected at the time of service and that my office does not bill nor accept insurance payments in order to prevent misunderstandings at check out.” She also declines requests to provide expert testimony for legal cases. “I’ve been in this business a long time, and every day I get requests to be an expert or to review a case involving a provider who may or may not have made a mistake. I really hate going down that rabbit hole.”
Another solution to keeping difficult patients in check is to collaborate with your entire office staff on how to best deal with them. “You need to present a united front with these patients: They’re going to divide and conquer, with complaints like, ‘How dare the doctor be so late. I’ve been waiting here for 30 minutes. Doesn’t she know I’m busy?’ ” Dr. Alster said. “You’re going to have to give them the tools to set limits as well. During our staff meetings, we review the upcoming patient schedule and identify potentially difficult situations in order to make sure the team is on the same page. Because my office is located in the power corridor of Washington [three blocks away from the White House] and my patient base is populated by prevalent personalities, expectations are extraordinarily high. As such, it is important that we set limits and rules that everyone can play by.”
Getting a sense of whether a patient is angry or manipulative can also help. An angry patient often holds an expectation that has been unmet, or harbors fears related to the treatment itself, she said, while a manipulative patient may engage in bullying, excessive flattery, or veiled threats. “They often expect specific treatments that have only worked for them in the past, even though it may be opposed to the treatment you recommend. They know better than you, even though you’re the expert.”
Communicating effectively with these two types of patients requires a slightly different approach. “With an angry patient, you want to share decision making,” Dr. Alster said. “Have them voice their concerns and come up with a plan together going forward. You’re not going to make that person less angry by telling them what to do.” The manipulative patient, meanwhile, requires a team approach. For example, she may ask your medical assistant for opinions on the treatment option you recommended during your office consultation with her, or second-guess your recommendation with that person altogether. “Everybody needs to know who the manipulative patients are and approach them as a team.”
The art of nonconfrontation
Dr. Alster brings a nonconfrontational approach to interactions with difficult patients. “You can apologize if you’ve kept them waiting, but you can’t apologize for everything all the time,” she said. “I may say something like, ‘I appreciate that your visit is running late. I apologize for the delay and want you to know that we take as much time as necessary for each patient and that unforeseen circumstances beyond our control sometimes arise.’ ” Another phrase she may use is, “I understand that this has been a stressful visit, but I want to talk to you about your experience and identify how we can improve subsequent appointments.”
Showing empathy never hurts. “Repeat back to them what you heard, and establish the fact that you understand,” Dr. Alster said. “Lower your voice, talk slowly, don’t get caught up in emotion. Otherwise, you’re going down in a sinkhole with them. Be wrong to be right. This encourages negotiation. You also want to document all patient interactions. Put every correspondence in the patient’s EMR.”
Dr. Alster advises clinicians to provide an outline of office policies and procedures to all patients, as well as written and verbal instructions related to their care. She also phones or emails patients undergoing a treatment for the first time. “Even if they’ve been in the practice for several years, if they received filler injections for the first time [instead of Botox], we still check in with those patients when they receive a first-time treatment to make sure they’re doing okay,” she said. “We’ll call them that evening or at the very least early the next morning to make sure that they don’t have any questions or concerns.”
If problems persist despite your best efforts, sometimes your best option is to dismiss difficult patients from your practice. “That’s only when everything else fails,” Dr. Alster said. “A concise termination letter should state a ‘breakdown in physician-patient relationship.’ I call it my ‘Dear John’ letter, and since 1990, I’ve only written six of these. A detailed explanation is usually not needed, but may be advisable depending on your state, to protect yourself from a liability standpoint. I instruct patients to contact the state medical society for referral to another provider and inform them that upon their written request, their medical records will be forwarded to their new provider. I also set up a reasonable timeline during which I will continue to see them for emergency visits to ensure that there is continuity of care, even when it is a cosmetic situation.”
Dr. Alster reported having no financial disclosures related to her presentation.
EXPERT ANALYSIS FROM ASLMS 2019
Treatment with gold microparticles plus lasers a viable option for acne
DENVER – Combining according to Jill S. Waibel, MD.
“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”
The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.
Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”
Energy was delivered at a fluency of 25-34 J/cm2 and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.
Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.
After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.
“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”
The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.
DENVER – Combining according to Jill S. Waibel, MD.
“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”
The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.
Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”
Energy was delivered at a fluency of 25-34 J/cm2 and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.
Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.
After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.
“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”
The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.
DENVER – Combining according to Jill S. Waibel, MD.
“Why do we need lasers and light for acne? We have compliance issues, particularly in the pubertal population,” she said at the annual conference of the American Society for Laser Medicine and Surgery. “We also have systemic side effects from medications and antibiotic resistance. Acne is still the number one reason people see a dermatologist.”
The gold microparticles were cleared by the Food and Drug Administration in September 2018 for the treatment of mild to moderate inflammatory acne. Based on European study data and ongoing studies in the United States, the optimal treatment approach begins with putting on a topical retinoid nightly and benzoyl peroxide (BPO) wash to clear follicular debris and reduce bacterial load prior to the application of gold microparticles and laser energy.
Dr. Waibel, director of the Miami Dermatology and Laser Institute, presented results from a clinical trial of 64 patients with mild to moderate acne that was conducted at seven European centers. All patients applied topical 0.1% adapalene/2.5% benzoyl peroxide daily for 2-4 weeks, then they underwent three microparticles plus laser procedures over a 2-week period. “It takes about 10 minutes to put the gold nanoparticles on,” Dr. Waibel said. “They’re rubbed in by a massager, the particles get in down into the follicle. Once it’s in the follicle, you wipe the gold completely off and you activate the FDA-approved 1064 nm Nd:YAG laser.”
Energy was delivered at a fluency of 25-34 J/cm2 and a pulse duration of 30 seconds. Concomitant rescue medications were allowed at the discretion of the investigator after the 2-month evaluation. Formal evaluations included inflammatory lesion counts at baseline, 2, 3, and 6 months; the Investigator Global Assessment scale at baseline, 2, 3, and 6 months; and safety and tolerability. Most of the patients (78%) were female, and their average age was 23 years, with a range between 13 and 38 years. The average level of pain reported by patients was 4 on a scale between 0 and 10, and mild, transient erythema and edema were reported post procedure. There were no adverse events otherwise.
Dr. Waibel reported that the interim mean improvement of inflammatory lesion counts was 66% at 3 months and 79% at 6 months. “At six months, 63% of patients were clear or almost clear according to the Investigator Global Assessment scale,” she added.
After the three treatment sessions, researchers observed a 63% reduction in acne at 2 months, a 74% reduction at 6 months, and an 85% reduction at 12 months. By comparison, a subset of 26 patients who received gold microparticle monotherapy had a 49% reduction in acne at 2 months and a 65% reduction at 6 months.
“A short course of retinoid and benzoyl peroxide prior to gold microparticles treatment improved the inflammatory lesion count reduction, compared with historical studies,” Dr. Waibel said (J Invest Dermatol. 2015;135[7]:1727-34). “Gold microparticles treatment for acne may be part of a multitherapy approach for patients with mild to moderate facial acne. Clinical outcomes are predictable and durable through 12 months.”
The approach is being further studied in the United States and researchers are exploring the potential for fewer treatments over a period of two weeks. Dr. Waibel disclosed that she has served on the advisory board for Sebacia, which developed the gold microparticles, and has received clinical trials funding from the company. She also reported having financial relationships with numerous other device and pharmaceutical companies.
REPORTING FROM ASLMS 2019
What does a Google search for cosmetic and laser procedures reveal?
DENVER – of professional societies only 8% of the time, and even less frequently to websites of academic centers and peer-reviewed medical journals, results from a novel study showed.
“An increasing number of patients are seeking information about cosmetic and laser dermatology from online sources,” Jennifer L. Sawaya, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “There are several studies that have discussed the role of the Internet and social media in dermatology. To our knowledge, this is the first study to specifically look at the results of Google search terms within our field to investigate which sources are providing this information.”
Dr. Sawaya, a fellow at Massachusetts General Hospital and the Wellman Center for Photomedicine, Boston, and her colleagues cross-measured keyword analytics provided by Zalea, an online resource on cosmetic treatments for consumers, with the most used Instagram hashtags to obtain 10 online keywords: body contouring, Botox, fillers, CoolSculpting, laser hair removal, tattoo removal, skin tightening, skin rejuvenation, cosmetic surgery, and liposuction. Next, they used an advanced Google search to obtain the top 25 search results for each of those 10 keywords and categorized information sources as professional societies, peer-reviewed journals, non–peer-reviewed online health information, news/media, device/cosmeceutical companies, clinical practices, academic centers, or medical spas.
Overall, the top search results came from clinical practices 23% of the time, followed by online health information sites (19%), medical spas (16%), and news/media (15%). A much smaller percentage of the search results came from professional societies (8%), academic centers (6%), and peer-reviewed medical journals (5%). Within the clinical practices and medical spas, nearly half of these sources were plastic surgeons, while board-certified dermatologists comprised only 21% of the clinical information sources.
When Dr. Sawaya and her associates evaluated the source of search results for each keyword, results varied. For example, search results for “body contouring” came most frequently from professional societies and clinical practices (20% each), “Botox” from news/media (36%), “fillers” from online health information (28%), “CoolSculpting” from clinical practices (40%), “laser hair removal” from news/media (32%), “tattoo removal” from medical spas (28%), “skin tightening” from news/media (24%), “skin rejuvenation” from medical spas (28%), “cosmetic surgery” from clinical practices (52%), and “liposuction” from online health information (36%).
“Our clinical take-home message is essentially a call for an increasing amount of evidence-based, academic content to be made available for online consumption,” Dr. Sawaya said. “In an era when patients seek a lot of medical information online and make important decisions through this manner, we have an obligation to understand what is out there and do our best to improve the quality of available information.”
She acknowledged certain limitations of the study, including the fact that results of a Google search may vary depending on the type of device used (mobile, desktop) as well as the location of the device. “An additional limitation is how the search history on the device may impact results,” she said. “To control for this, the device history, cache, and cookies were cleared prior to the search. Despite these controls, it is unclear how and to what extent prior searches affect the Google ranking algorithm. We acknowledge that the findings in this study reflect a single point in time and that the results of a Google search will change dynamically based on many factors. Finally, we acknowledge that our study is based on a single search engine site and that the trends we observe with Google may not be extrapolated to other online channels.”
Dr. Sawaya reported having no financial disclosures.
DENVER – of professional societies only 8% of the time, and even less frequently to websites of academic centers and peer-reviewed medical journals, results from a novel study showed.
“An increasing number of patients are seeking information about cosmetic and laser dermatology from online sources,” Jennifer L. Sawaya, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “There are several studies that have discussed the role of the Internet and social media in dermatology. To our knowledge, this is the first study to specifically look at the results of Google search terms within our field to investigate which sources are providing this information.”
Dr. Sawaya, a fellow at Massachusetts General Hospital and the Wellman Center for Photomedicine, Boston, and her colleagues cross-measured keyword analytics provided by Zalea, an online resource on cosmetic treatments for consumers, with the most used Instagram hashtags to obtain 10 online keywords: body contouring, Botox, fillers, CoolSculpting, laser hair removal, tattoo removal, skin tightening, skin rejuvenation, cosmetic surgery, and liposuction. Next, they used an advanced Google search to obtain the top 25 search results for each of those 10 keywords and categorized information sources as professional societies, peer-reviewed journals, non–peer-reviewed online health information, news/media, device/cosmeceutical companies, clinical practices, academic centers, or medical spas.
Overall, the top search results came from clinical practices 23% of the time, followed by online health information sites (19%), medical spas (16%), and news/media (15%). A much smaller percentage of the search results came from professional societies (8%), academic centers (6%), and peer-reviewed medical journals (5%). Within the clinical practices and medical spas, nearly half of these sources were plastic surgeons, while board-certified dermatologists comprised only 21% of the clinical information sources.
When Dr. Sawaya and her associates evaluated the source of search results for each keyword, results varied. For example, search results for “body contouring” came most frequently from professional societies and clinical practices (20% each), “Botox” from news/media (36%), “fillers” from online health information (28%), “CoolSculpting” from clinical practices (40%), “laser hair removal” from news/media (32%), “tattoo removal” from medical spas (28%), “skin tightening” from news/media (24%), “skin rejuvenation” from medical spas (28%), “cosmetic surgery” from clinical practices (52%), and “liposuction” from online health information (36%).
“Our clinical take-home message is essentially a call for an increasing amount of evidence-based, academic content to be made available for online consumption,” Dr. Sawaya said. “In an era when patients seek a lot of medical information online and make important decisions through this manner, we have an obligation to understand what is out there and do our best to improve the quality of available information.”
She acknowledged certain limitations of the study, including the fact that results of a Google search may vary depending on the type of device used (mobile, desktop) as well as the location of the device. “An additional limitation is how the search history on the device may impact results,” she said. “To control for this, the device history, cache, and cookies were cleared prior to the search. Despite these controls, it is unclear how and to what extent prior searches affect the Google ranking algorithm. We acknowledge that the findings in this study reflect a single point in time and that the results of a Google search will change dynamically based on many factors. Finally, we acknowledge that our study is based on a single search engine site and that the trends we observe with Google may not be extrapolated to other online channels.”
Dr. Sawaya reported having no financial disclosures.
DENVER – of professional societies only 8% of the time, and even less frequently to websites of academic centers and peer-reviewed medical journals, results from a novel study showed.
“An increasing number of patients are seeking information about cosmetic and laser dermatology from online sources,” Jennifer L. Sawaya, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “There are several studies that have discussed the role of the Internet and social media in dermatology. To our knowledge, this is the first study to specifically look at the results of Google search terms within our field to investigate which sources are providing this information.”
Dr. Sawaya, a fellow at Massachusetts General Hospital and the Wellman Center for Photomedicine, Boston, and her colleagues cross-measured keyword analytics provided by Zalea, an online resource on cosmetic treatments for consumers, with the most used Instagram hashtags to obtain 10 online keywords: body contouring, Botox, fillers, CoolSculpting, laser hair removal, tattoo removal, skin tightening, skin rejuvenation, cosmetic surgery, and liposuction. Next, they used an advanced Google search to obtain the top 25 search results for each of those 10 keywords and categorized information sources as professional societies, peer-reviewed journals, non–peer-reviewed online health information, news/media, device/cosmeceutical companies, clinical practices, academic centers, or medical spas.
Overall, the top search results came from clinical practices 23% of the time, followed by online health information sites (19%), medical spas (16%), and news/media (15%). A much smaller percentage of the search results came from professional societies (8%), academic centers (6%), and peer-reviewed medical journals (5%). Within the clinical practices and medical spas, nearly half of these sources were plastic surgeons, while board-certified dermatologists comprised only 21% of the clinical information sources.
When Dr. Sawaya and her associates evaluated the source of search results for each keyword, results varied. For example, search results for “body contouring” came most frequently from professional societies and clinical practices (20% each), “Botox” from news/media (36%), “fillers” from online health information (28%), “CoolSculpting” from clinical practices (40%), “laser hair removal” from news/media (32%), “tattoo removal” from medical spas (28%), “skin tightening” from news/media (24%), “skin rejuvenation” from medical spas (28%), “cosmetic surgery” from clinical practices (52%), and “liposuction” from online health information (36%).
“Our clinical take-home message is essentially a call for an increasing amount of evidence-based, academic content to be made available for online consumption,” Dr. Sawaya said. “In an era when patients seek a lot of medical information online and make important decisions through this manner, we have an obligation to understand what is out there and do our best to improve the quality of available information.”
She acknowledged certain limitations of the study, including the fact that results of a Google search may vary depending on the type of device used (mobile, desktop) as well as the location of the device. “An additional limitation is how the search history on the device may impact results,” she said. “To control for this, the device history, cache, and cookies were cleared prior to the search. Despite these controls, it is unclear how and to what extent prior searches affect the Google ranking algorithm. We acknowledge that the findings in this study reflect a single point in time and that the results of a Google search will change dynamically based on many factors. Finally, we acknowledge that our study is based on a single search engine site and that the trends we observe with Google may not be extrapolated to other online channels.”
Dr. Sawaya reported having no financial disclosures.
REPORTING FROM ASLMS 2019
Key clinical point: There is a paucity of online information regarding cosmetic and laser dermatology from professional societies and academic, peer-reviewed sources.
Major finding: Top Google search results came from clinical practices 23% of the time and from professional societies only 8% of the time.
Study details: An online review of 25 Google search results for 10 keywords associated with cosmetic and laser dermatology.
Disclosures: Dr. Sawaya reported having no financial disclosures.
Study finds pain perception disconnect during vascular laser procedures
DENVER – There is an apparent disconnect between the level of periprocedural pain experienced by patients during vascular laser procedures and what device manufacturers say that level of pain should be, results from a retrospective study showed.
“Although there is an abundance of research on how pain signals are transmitted in the nervous system and how pain is perceived among certain patient demographics, there is not much known about how pain perception differs from that put forth by industry,” Lauren Bonati, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “This study is unique because we are questioning not whether pain perception is reproducible between patients, but rather if it reflects what industry and device manufacturers are telling us.”
Dr. Bonati, a dermatologist at Edwards, Colo.–based Mountain Dermatology Specialists, and her colleagues collected median and mode pain scores from a past clinical trial that investigated a dual wavelength laser used for different types of treatments. “The treatment type (laser wavelength and treatment area) was largely based on the severity of facial redness for each individual patient,” she explained. “The options were spot treatment, nose and cheeks, or a global facial treatment with either wavelength.” The researchers reviewed industry-provided materials to determine language regarding procedural pain, and they interviewed the clinical trial’s principal investigator about how pain expectations were set during the trial. Next, they transferred subject-reported pain scores and verbal pain descriptors to the validated Numerical Rating Scale and the Verbal Rating Scale, for comparison.
In all, 85 procedural pain scores were collected from 22 subject charts. The researchers found that the average procedural pain scores for treatment types reported by subjects were translated to entirely different verbal and numerical categories of pain from those described by industry materials. “It was surprising to see how vague pain descriptions can be in device manuals and industry materials, if even addressed at all,” Dr. Bonati said.
She advised clinicians to be wary of whom they rely on for information related to pain expectations. “Also, remember that wrongly set pain expectations can have physiologic and emotional effects that may positively or negatively impact patient experience,” Dr. Bonati said.
She acknowledged certain limitations of the study, including the fact that it was a review of a previously conducted clinical trial, “which is not a perfect representation of real-life clinic.”
She reported having no conflicts of interest.
DENVER – There is an apparent disconnect between the level of periprocedural pain experienced by patients during vascular laser procedures and what device manufacturers say that level of pain should be, results from a retrospective study showed.
“Although there is an abundance of research on how pain signals are transmitted in the nervous system and how pain is perceived among certain patient demographics, there is not much known about how pain perception differs from that put forth by industry,” Lauren Bonati, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “This study is unique because we are questioning not whether pain perception is reproducible between patients, but rather if it reflects what industry and device manufacturers are telling us.”
Dr. Bonati, a dermatologist at Edwards, Colo.–based Mountain Dermatology Specialists, and her colleagues collected median and mode pain scores from a past clinical trial that investigated a dual wavelength laser used for different types of treatments. “The treatment type (laser wavelength and treatment area) was largely based on the severity of facial redness for each individual patient,” she explained. “The options were spot treatment, nose and cheeks, or a global facial treatment with either wavelength.” The researchers reviewed industry-provided materials to determine language regarding procedural pain, and they interviewed the clinical trial’s principal investigator about how pain expectations were set during the trial. Next, they transferred subject-reported pain scores and verbal pain descriptors to the validated Numerical Rating Scale and the Verbal Rating Scale, for comparison.
In all, 85 procedural pain scores were collected from 22 subject charts. The researchers found that the average procedural pain scores for treatment types reported by subjects were translated to entirely different verbal and numerical categories of pain from those described by industry materials. “It was surprising to see how vague pain descriptions can be in device manuals and industry materials, if even addressed at all,” Dr. Bonati said.
She advised clinicians to be wary of whom they rely on for information related to pain expectations. “Also, remember that wrongly set pain expectations can have physiologic and emotional effects that may positively or negatively impact patient experience,” Dr. Bonati said.
She acknowledged certain limitations of the study, including the fact that it was a review of a previously conducted clinical trial, “which is not a perfect representation of real-life clinic.”
She reported having no conflicts of interest.
DENVER – There is an apparent disconnect between the level of periprocedural pain experienced by patients during vascular laser procedures and what device manufacturers say that level of pain should be, results from a retrospective study showed.
“Although there is an abundance of research on how pain signals are transmitted in the nervous system and how pain is perceived among certain patient demographics, there is not much known about how pain perception differs from that put forth by industry,” Lauren Bonati, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “This study is unique because we are questioning not whether pain perception is reproducible between patients, but rather if it reflects what industry and device manufacturers are telling us.”
Dr. Bonati, a dermatologist at Edwards, Colo.–based Mountain Dermatology Specialists, and her colleagues collected median and mode pain scores from a past clinical trial that investigated a dual wavelength laser used for different types of treatments. “The treatment type (laser wavelength and treatment area) was largely based on the severity of facial redness for each individual patient,” she explained. “The options were spot treatment, nose and cheeks, or a global facial treatment with either wavelength.” The researchers reviewed industry-provided materials to determine language regarding procedural pain, and they interviewed the clinical trial’s principal investigator about how pain expectations were set during the trial. Next, they transferred subject-reported pain scores and verbal pain descriptors to the validated Numerical Rating Scale and the Verbal Rating Scale, for comparison.
In all, 85 procedural pain scores were collected from 22 subject charts. The researchers found that the average procedural pain scores for treatment types reported by subjects were translated to entirely different verbal and numerical categories of pain from those described by industry materials. “It was surprising to see how vague pain descriptions can be in device manuals and industry materials, if even addressed at all,” Dr. Bonati said.
She advised clinicians to be wary of whom they rely on for information related to pain expectations. “Also, remember that wrongly set pain expectations can have physiologic and emotional effects that may positively or negatively impact patient experience,” Dr. Bonati said.
She acknowledged certain limitations of the study, including the fact that it was a review of a previously conducted clinical trial, “which is not a perfect representation of real-life clinic.”
She reported having no conflicts of interest.
REPORTING FROM ASLMS 2019
Key clinical point: Industry-provided materials failed to capture the range of procedural pain scores reported by patients undergoing a variety of vascular laser procedures.
Major finding: The average procedural pain scores for treatment types reported by subjects were translated to entirely different verbal and numerical categories of pain from those described by industry materials.
Study details: A retrospective evaluation of 85 procedural pain scores collected from 22 subject charts.
Disclosures: Dr. Bonati reported having no financial disclosures.
Investigative magnetic device found effective for skin tightening in a small study
DENVER – Patients treated with results from a small trial showed.
“There are many different modalities for tissue tightening, including lights, radiofrequency, ultrasound and thermal energy,” Jerome M. Garden, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The idea behind all of these technologies is to heat up the skin’s collagen and to stimulate further collagen production, which can then result in improved skin tightening and textural improvement.”
In a trial conducted at the Chicago-based Physicians Laser and Dermatology Institute, Dr. Garden and his colleagues evaluated a new technology for tissue tightening that involves magnetic energy. Developed by Rocky Mountain Biosystems and BioFusionary Corp., the investigative device produces a magnetic field in the targeted tissue, which then results in the heating and eventual tightening of the tissue. “By using magnetic energy, which relies on the polarity of the molecules, it allows for a safe way to target specifically the polar dermis, without heating the relatively dry epidermis or nonpolar adipose layer, resulting in a more tolerable and potentially safer alternative to tissue tightening,” said Dr. Garden, a dermatologist who is the director of the Physicians Laser and Dermatology Institute.
For the trial, 20 patients with facial and upper skin laxity underwent a mean of 4.3 treatment sessions with the 27MHz magnetic device that used a 3-cm spot size, with a minimum of 4 weeks between each session. No anesthetics or analgesics were used. “No gels or skin prep was performed before the treatment, other than a gentle soap beforehand,” Dr. Garden said. “A bland moisturizer was applied to the treated skin after treatments.” The majority of patients (85%) had paid for their procedures (a price comparable to other skin-tightening procedures), and two board-certified dermatologists evaluated both before and after photographs for overall improvement of skin laxity and texture. Follow-ups were done 2-4 months after the last treatment. The observers were not informed which photographs were before or after.
Dr. Garden reported that the observers correctly chose 19 out of 20 patients’ before and after photographs, and they rated the mean grade level of improvement as 43%. Nearly half of the patients (48%) were graded at 50% or greater improvement. At the same time, patients rated their own improvement as a mean 6.5 out of 10. Nearly half of patients graded their outcome at 7 or better, which was designated as “very satisfied.” The procedures were well tolerated, Dr. Garden said, and the most common side effects were minor transient erythema and edema. The erythema generally faded after 2-4 hours, and the mild edema lasted up to 24 hours.
“Magnetic energy is a new technology that can be used to treat lower face and neck laxity,” said Dr. Garden, who is also a professor of clinical dermatology at Northwestern University, Chicago. “We only treated patients with skin types I-IV, but we feel that this technology is likely safe for higher skin types as well.”
Rocky Mountain Biosystems and BioFusionary Corp. provided the device used for the study. Dr. Garden and his colleagues are currently extending the ongoing trial. He reported having no financial disclosures.
DENVER – Patients treated with results from a small trial showed.
“There are many different modalities for tissue tightening, including lights, radiofrequency, ultrasound and thermal energy,” Jerome M. Garden, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The idea behind all of these technologies is to heat up the skin’s collagen and to stimulate further collagen production, which can then result in improved skin tightening and textural improvement.”
In a trial conducted at the Chicago-based Physicians Laser and Dermatology Institute, Dr. Garden and his colleagues evaluated a new technology for tissue tightening that involves magnetic energy. Developed by Rocky Mountain Biosystems and BioFusionary Corp., the investigative device produces a magnetic field in the targeted tissue, which then results in the heating and eventual tightening of the tissue. “By using magnetic energy, which relies on the polarity of the molecules, it allows for a safe way to target specifically the polar dermis, without heating the relatively dry epidermis or nonpolar adipose layer, resulting in a more tolerable and potentially safer alternative to tissue tightening,” said Dr. Garden, a dermatologist who is the director of the Physicians Laser and Dermatology Institute.
For the trial, 20 patients with facial and upper skin laxity underwent a mean of 4.3 treatment sessions with the 27MHz magnetic device that used a 3-cm spot size, with a minimum of 4 weeks between each session. No anesthetics or analgesics were used. “No gels or skin prep was performed before the treatment, other than a gentle soap beforehand,” Dr. Garden said. “A bland moisturizer was applied to the treated skin after treatments.” The majority of patients (85%) had paid for their procedures (a price comparable to other skin-tightening procedures), and two board-certified dermatologists evaluated both before and after photographs for overall improvement of skin laxity and texture. Follow-ups were done 2-4 months after the last treatment. The observers were not informed which photographs were before or after.
Dr. Garden reported that the observers correctly chose 19 out of 20 patients’ before and after photographs, and they rated the mean grade level of improvement as 43%. Nearly half of the patients (48%) were graded at 50% or greater improvement. At the same time, patients rated their own improvement as a mean 6.5 out of 10. Nearly half of patients graded their outcome at 7 or better, which was designated as “very satisfied.” The procedures were well tolerated, Dr. Garden said, and the most common side effects were minor transient erythema and edema. The erythema generally faded after 2-4 hours, and the mild edema lasted up to 24 hours.
“Magnetic energy is a new technology that can be used to treat lower face and neck laxity,” said Dr. Garden, who is also a professor of clinical dermatology at Northwestern University, Chicago. “We only treated patients with skin types I-IV, but we feel that this technology is likely safe for higher skin types as well.”
Rocky Mountain Biosystems and BioFusionary Corp. provided the device used for the study. Dr. Garden and his colleagues are currently extending the ongoing trial. He reported having no financial disclosures.
DENVER – Patients treated with results from a small trial showed.
“There are many different modalities for tissue tightening, including lights, radiofrequency, ultrasound and thermal energy,” Jerome M. Garden, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The idea behind all of these technologies is to heat up the skin’s collagen and to stimulate further collagen production, which can then result in improved skin tightening and textural improvement.”
In a trial conducted at the Chicago-based Physicians Laser and Dermatology Institute, Dr. Garden and his colleagues evaluated a new technology for tissue tightening that involves magnetic energy. Developed by Rocky Mountain Biosystems and BioFusionary Corp., the investigative device produces a magnetic field in the targeted tissue, which then results in the heating and eventual tightening of the tissue. “By using magnetic energy, which relies on the polarity of the molecules, it allows for a safe way to target specifically the polar dermis, without heating the relatively dry epidermis or nonpolar adipose layer, resulting in a more tolerable and potentially safer alternative to tissue tightening,” said Dr. Garden, a dermatologist who is the director of the Physicians Laser and Dermatology Institute.
For the trial, 20 patients with facial and upper skin laxity underwent a mean of 4.3 treatment sessions with the 27MHz magnetic device that used a 3-cm spot size, with a minimum of 4 weeks between each session. No anesthetics or analgesics were used. “No gels or skin prep was performed before the treatment, other than a gentle soap beforehand,” Dr. Garden said. “A bland moisturizer was applied to the treated skin after treatments.” The majority of patients (85%) had paid for their procedures (a price comparable to other skin-tightening procedures), and two board-certified dermatologists evaluated both before and after photographs for overall improvement of skin laxity and texture. Follow-ups were done 2-4 months after the last treatment. The observers were not informed which photographs were before or after.
Dr. Garden reported that the observers correctly chose 19 out of 20 patients’ before and after photographs, and they rated the mean grade level of improvement as 43%. Nearly half of the patients (48%) were graded at 50% or greater improvement. At the same time, patients rated their own improvement as a mean 6.5 out of 10. Nearly half of patients graded their outcome at 7 or better, which was designated as “very satisfied.” The procedures were well tolerated, Dr. Garden said, and the most common side effects were minor transient erythema and edema. The erythema generally faded after 2-4 hours, and the mild edema lasted up to 24 hours.
“Magnetic energy is a new technology that can be used to treat lower face and neck laxity,” said Dr. Garden, who is also a professor of clinical dermatology at Northwestern University, Chicago. “We only treated patients with skin types I-IV, but we feel that this technology is likely safe for higher skin types as well.”
Rocky Mountain Biosystems and BioFusionary Corp. provided the device used for the study. Dr. Garden and his colleagues are currently extending the ongoing trial. He reported having no financial disclosures.
REPORTING FROM ASLMS 2019
Key clinical point: A device that delivers high magnetic energy was found safe and effective for treatment of skin laxity.
Major finding: Following treatment, dermatologists graded nearly half of the patients (48%) at 50% or greater improvement.
Study details: A single-center trial of 20 patients with facial and upper skin laxity who underwent a mean of 4.3 treatment sessions.
Disclosures: Rocky Mountain Biosystems and BioFusionary Corp. provided the device used for the study. Dr. Garden reported having no financial disclosures.
At what diameter does a scar form after a full-thickness wound?
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
REPORTING FROM ASLMS 2019
Key clinical point: Collecting skin microbiopsies of different sizes from preabdominoplasty skin is safe and highly tolerable.
Major finding: Full-thickness skin wounds greater than 400-500 mcm in diameter heal with a clinically identifiable scar.
Study details: A pilot trial in five individuals that set out to determine the biopsy size limit at which healing occurs without a scar, as well as demonstrate the safety of performing multiple skin microbiopsies.
Disclosures: Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
More than 1 in 10 dermatology residents report laser-associated adverse events in training
DENVER –
“Incorporating a formal laser safety education curriculum is an opportunity for residency programs and organizations like ASLMS,” study coauthor Daniel J. Bergman, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery.
In what is believed to be the first study of its kind, Dr. Bergman and his coauthor Shari A. Ochoa, MD, created an online survey intended to evaluate the safety education and number of adverse laser-associated events that occurred during dermatology residencies in the United States. After the coauthors sought input for content of the survey from dermatology faculty and their colleagues at the Mayo Clinic in Scottsdale, Ariz., they used the Association of Professors of Dermatology email database to distribute the survey to Accreditation Council for Graduate Medical Education (ACGME)–approved dermatology residency programs. “In general, most studies evaluate the models of education and the number of hours dedicated to learning a skill,” said Dr. Bergman, who is a first-year dermatology resident at the Mayo Clinic. “This study is unique because it identified adverse events experienced by dermatology residents and also evaluated their formal laser safety training.”
To date, 78 dermatology residents have completed responses to the survey. Of these, 10 (13%) identified an adverse event associated with use of a laser. Of those respondents, six respondents knew how to report the event, five felt comfortable operating the laser, three had formal laser safety training, five felt like they understood the risks associated with lasers, and all but one felt properly supervised. One identified plans for postresidency laser training. Of the 68 respondents who have not identified an adverse event, 39 (57%) reported formal laser safety training, and only 24 (35%) indicated that they knew how to report an adverse event.
“I was interested to find that 13% of dermatology residents have already experienced an adverse laser event,” Dr. Bergman said. “I was also surprised to discover that only 54% of all survey respondents identified or recognized formal laser safety training. The ACGME mandates that dermatology residents receive training in the theoretical and practical applications of lasers. This finding may indicate that additional training, focusing on laser safety, should be incorporated more formally into the curriculum at some programs.”
He acknowledged certain limitations of the study, including the relatively small number of respondents and the fact that only ACGME-accredited residencies were asked to participate. “Therefore, we are still missing a large amount of data,” Dr. Bergman said. “Most notably, the results are subject to recall bias and participants defined the nature of an adverse laser event.”
He reported having no financial disclosures.
DENVER –
“Incorporating a formal laser safety education curriculum is an opportunity for residency programs and organizations like ASLMS,” study coauthor Daniel J. Bergman, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery.
In what is believed to be the first study of its kind, Dr. Bergman and his coauthor Shari A. Ochoa, MD, created an online survey intended to evaluate the safety education and number of adverse laser-associated events that occurred during dermatology residencies in the United States. After the coauthors sought input for content of the survey from dermatology faculty and their colleagues at the Mayo Clinic in Scottsdale, Ariz., they used the Association of Professors of Dermatology email database to distribute the survey to Accreditation Council for Graduate Medical Education (ACGME)–approved dermatology residency programs. “In general, most studies evaluate the models of education and the number of hours dedicated to learning a skill,” said Dr. Bergman, who is a first-year dermatology resident at the Mayo Clinic. “This study is unique because it identified adverse events experienced by dermatology residents and also evaluated their formal laser safety training.”
To date, 78 dermatology residents have completed responses to the survey. Of these, 10 (13%) identified an adverse event associated with use of a laser. Of those respondents, six respondents knew how to report the event, five felt comfortable operating the laser, three had formal laser safety training, five felt like they understood the risks associated with lasers, and all but one felt properly supervised. One identified plans for postresidency laser training. Of the 68 respondents who have not identified an adverse event, 39 (57%) reported formal laser safety training, and only 24 (35%) indicated that they knew how to report an adverse event.
“I was interested to find that 13% of dermatology residents have already experienced an adverse laser event,” Dr. Bergman said. “I was also surprised to discover that only 54% of all survey respondents identified or recognized formal laser safety training. The ACGME mandates that dermatology residents receive training in the theoretical and practical applications of lasers. This finding may indicate that additional training, focusing on laser safety, should be incorporated more formally into the curriculum at some programs.”
He acknowledged certain limitations of the study, including the relatively small number of respondents and the fact that only ACGME-accredited residencies were asked to participate. “Therefore, we are still missing a large amount of data,” Dr. Bergman said. “Most notably, the results are subject to recall bias and participants defined the nature of an adverse laser event.”
He reported having no financial disclosures.
DENVER –
“Incorporating a formal laser safety education curriculum is an opportunity for residency programs and organizations like ASLMS,” study coauthor Daniel J. Bergman, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery.
In what is believed to be the first study of its kind, Dr. Bergman and his coauthor Shari A. Ochoa, MD, created an online survey intended to evaluate the safety education and number of adverse laser-associated events that occurred during dermatology residencies in the United States. After the coauthors sought input for content of the survey from dermatology faculty and their colleagues at the Mayo Clinic in Scottsdale, Ariz., they used the Association of Professors of Dermatology email database to distribute the survey to Accreditation Council for Graduate Medical Education (ACGME)–approved dermatology residency programs. “In general, most studies evaluate the models of education and the number of hours dedicated to learning a skill,” said Dr. Bergman, who is a first-year dermatology resident at the Mayo Clinic. “This study is unique because it identified adverse events experienced by dermatology residents and also evaluated their formal laser safety training.”
To date, 78 dermatology residents have completed responses to the survey. Of these, 10 (13%) identified an adverse event associated with use of a laser. Of those respondents, six respondents knew how to report the event, five felt comfortable operating the laser, three had formal laser safety training, five felt like they understood the risks associated with lasers, and all but one felt properly supervised. One identified plans for postresidency laser training. Of the 68 respondents who have not identified an adverse event, 39 (57%) reported formal laser safety training, and only 24 (35%) indicated that they knew how to report an adverse event.
“I was interested to find that 13% of dermatology residents have already experienced an adverse laser event,” Dr. Bergman said. “I was also surprised to discover that only 54% of all survey respondents identified or recognized formal laser safety training. The ACGME mandates that dermatology residents receive training in the theoretical and practical applications of lasers. This finding may indicate that additional training, focusing on laser safety, should be incorporated more formally into the curriculum at some programs.”
He acknowledged certain limitations of the study, including the relatively small number of respondents and the fact that only ACGME-accredited residencies were asked to participate. “Therefore, we are still missing a large amount of data,” Dr. Bergman said. “Most notably, the results are subject to recall bias and participants defined the nature of an adverse laser event.”
He reported having no financial disclosures.
REPORTING FROM ASLMS 2019
Key clinical point: Laser-associated adverse events experienced by dermatology residents are not uncommon.
Major finding: Of 78 dermatology residents, 10 (13%) identified an adverse events associated with use of a laser.
Study details: An online survey of 78 dermatology residents.
Disclosures: Dr. Bergman reported having no financial disclosures.
Imaging mass cytometry sheds light on inflammation, demyelination in MS
DALLAS – Imaging mass cytometry is helping researchers to better understand how meningeal inflammation relates to cortical pathology in a subset of multiple sclerosis patients.
This technique for examining multiple proteins within intact tissue and distinguishing cell types based on complex combinations of markers has helped to spot evidence of meningeal inflammation in areas of patient brain samples with cortical gray matter lesions, confirming demyelination and meningeal inflammation observed in experimental allergic encephalomyelitis mouse models.
Imaging mass cytometry “allows us to potentially discriminate microglia from macrophages within brain lesions,” Jennifer Gommerman, PhD, said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We can look at lymphocytes as well. There’s a lot of potential with this technique, and we’re excited to apply it to the meningeal inflammatory sections of the brain.”
Dr. Gommerman, professor of immunology at the University of Toronto, noted that multiple sclerosis (MS) begins often with a relapsing form of the disease, which tracks with deep white matter lesions that clinicians can image with MRI. “But as the disease progresses, we know that pathology can change, and we can see more pathology in the cortex, including varied bands of demyelination that are adjacent to the meninges,” she said. “This phase of the disease is not effectively treated by therapeutics.”
In this later phase of the disease, she continued, “it’s thought perhaps that the immune system isn’t playing such a big role, but there has been a fair bit of evidence in the literature in recent years that there are in fact immune cells in the brains of people with progressive MS. You can find them in the meninges. They can form clusters of cells within the meninges and they tend to be adjacent to areas of cortical demyelination, suggesting they might be involved in this pathology.”
Dr. Gommerman and her colleagues developed an animal model to evaluate meningeal inflammation in an effort to determine if they can model cortical injury and disease progression. They used an adoptive transfer form of experimental allergic encephalomyelitis in which they prime T cells in SJL mice, remove them, polarize them toward a Th17 phenotype, and transfer them into naive recipients. “When we do this we can see clusters of immune cells forming in the meninges,” Dr. Gommerman said. “They start with T cells but then become overwhelmingly populated by B cells.” Adjacent to these clusters they noted disruption of the glia limitans and demyelination in the cortex. “There’s clearly something going on in the cortex of these animals.”
Mindful that age is one of the most significant predictors of disease progression, the researchers transferred young T cells into mice that were 6-8 months old in addition to animals that were 6-8 weeks old. “Upon sacrifice, the younger mice that got the young T cells had largely resolved their cortical pathology, while the old mice that got the young T cells still showed evidence of demyelination, very angry microglia, and a continual disruption of the glial limitans,” Dr. Gommerman said. “We were able to see axonal stress in comparison to the young mice. We also saw some evidence of synapse loss. It seems that these animals not only have demyelination in the cortex, but there are problems with the axons and the synapses.”
To apply this model in humans, she and her colleagues collaborated with Netherlands Brain Bank in order to obtain brain samples for analysis with imaging mass cytometry, which provides a time-of-flight mass spectrometry readout of the staining pattern of heavy metal ion–tagged antibodies on a single slide-mounted tissue section.
“We really have to be careful which [brain] samples we choose, because not all samples from progressive MS patients have evidence of meningeal inflammation,” she noted. So far, they have observed that meningeal inflammation is associated with gray matter lesions, rather than with normal-appearing gray matter.
“We also need to look at appropriate controls, so our plan is to look at patients who have meningeal inflammation but do not have MS,” she said.
Dr. Gommerman reported having received grants from Novartis, Roche, and Merck, as well as a consulting agreement with Roche.
DALLAS – Imaging mass cytometry is helping researchers to better understand how meningeal inflammation relates to cortical pathology in a subset of multiple sclerosis patients.
This technique for examining multiple proteins within intact tissue and distinguishing cell types based on complex combinations of markers has helped to spot evidence of meningeal inflammation in areas of patient brain samples with cortical gray matter lesions, confirming demyelination and meningeal inflammation observed in experimental allergic encephalomyelitis mouse models.
Imaging mass cytometry “allows us to potentially discriminate microglia from macrophages within brain lesions,” Jennifer Gommerman, PhD, said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We can look at lymphocytes as well. There’s a lot of potential with this technique, and we’re excited to apply it to the meningeal inflammatory sections of the brain.”
Dr. Gommerman, professor of immunology at the University of Toronto, noted that multiple sclerosis (MS) begins often with a relapsing form of the disease, which tracks with deep white matter lesions that clinicians can image with MRI. “But as the disease progresses, we know that pathology can change, and we can see more pathology in the cortex, including varied bands of demyelination that are adjacent to the meninges,” she said. “This phase of the disease is not effectively treated by therapeutics.”
In this later phase of the disease, she continued, “it’s thought perhaps that the immune system isn’t playing such a big role, but there has been a fair bit of evidence in the literature in recent years that there are in fact immune cells in the brains of people with progressive MS. You can find them in the meninges. They can form clusters of cells within the meninges and they tend to be adjacent to areas of cortical demyelination, suggesting they might be involved in this pathology.”
Dr. Gommerman and her colleagues developed an animal model to evaluate meningeal inflammation in an effort to determine if they can model cortical injury and disease progression. They used an adoptive transfer form of experimental allergic encephalomyelitis in which they prime T cells in SJL mice, remove them, polarize them toward a Th17 phenotype, and transfer them into naive recipients. “When we do this we can see clusters of immune cells forming in the meninges,” Dr. Gommerman said. “They start with T cells but then become overwhelmingly populated by B cells.” Adjacent to these clusters they noted disruption of the glia limitans and demyelination in the cortex. “There’s clearly something going on in the cortex of these animals.”
Mindful that age is one of the most significant predictors of disease progression, the researchers transferred young T cells into mice that were 6-8 months old in addition to animals that were 6-8 weeks old. “Upon sacrifice, the younger mice that got the young T cells had largely resolved their cortical pathology, while the old mice that got the young T cells still showed evidence of demyelination, very angry microglia, and a continual disruption of the glial limitans,” Dr. Gommerman said. “We were able to see axonal stress in comparison to the young mice. We also saw some evidence of synapse loss. It seems that these animals not only have demyelination in the cortex, but there are problems with the axons and the synapses.”
To apply this model in humans, she and her colleagues collaborated with Netherlands Brain Bank in order to obtain brain samples for analysis with imaging mass cytometry, which provides a time-of-flight mass spectrometry readout of the staining pattern of heavy metal ion–tagged antibodies on a single slide-mounted tissue section.
“We really have to be careful which [brain] samples we choose, because not all samples from progressive MS patients have evidence of meningeal inflammation,” she noted. So far, they have observed that meningeal inflammation is associated with gray matter lesions, rather than with normal-appearing gray matter.
“We also need to look at appropriate controls, so our plan is to look at patients who have meningeal inflammation but do not have MS,” she said.
Dr. Gommerman reported having received grants from Novartis, Roche, and Merck, as well as a consulting agreement with Roche.
DALLAS – Imaging mass cytometry is helping researchers to better understand how meningeal inflammation relates to cortical pathology in a subset of multiple sclerosis patients.
This technique for examining multiple proteins within intact tissue and distinguishing cell types based on complex combinations of markers has helped to spot evidence of meningeal inflammation in areas of patient brain samples with cortical gray matter lesions, confirming demyelination and meningeal inflammation observed in experimental allergic encephalomyelitis mouse models.
Imaging mass cytometry “allows us to potentially discriminate microglia from macrophages within brain lesions,” Jennifer Gommerman, PhD, said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We can look at lymphocytes as well. There’s a lot of potential with this technique, and we’re excited to apply it to the meningeal inflammatory sections of the brain.”
Dr. Gommerman, professor of immunology at the University of Toronto, noted that multiple sclerosis (MS) begins often with a relapsing form of the disease, which tracks with deep white matter lesions that clinicians can image with MRI. “But as the disease progresses, we know that pathology can change, and we can see more pathology in the cortex, including varied bands of demyelination that are adjacent to the meninges,” she said. “This phase of the disease is not effectively treated by therapeutics.”
In this later phase of the disease, she continued, “it’s thought perhaps that the immune system isn’t playing such a big role, but there has been a fair bit of evidence in the literature in recent years that there are in fact immune cells in the brains of people with progressive MS. You can find them in the meninges. They can form clusters of cells within the meninges and they tend to be adjacent to areas of cortical demyelination, suggesting they might be involved in this pathology.”
Dr. Gommerman and her colleagues developed an animal model to evaluate meningeal inflammation in an effort to determine if they can model cortical injury and disease progression. They used an adoptive transfer form of experimental allergic encephalomyelitis in which they prime T cells in SJL mice, remove them, polarize them toward a Th17 phenotype, and transfer them into naive recipients. “When we do this we can see clusters of immune cells forming in the meninges,” Dr. Gommerman said. “They start with T cells but then become overwhelmingly populated by B cells.” Adjacent to these clusters they noted disruption of the glia limitans and demyelination in the cortex. “There’s clearly something going on in the cortex of these animals.”
Mindful that age is one of the most significant predictors of disease progression, the researchers transferred young T cells into mice that were 6-8 months old in addition to animals that were 6-8 weeks old. “Upon sacrifice, the younger mice that got the young T cells had largely resolved their cortical pathology, while the old mice that got the young T cells still showed evidence of demyelination, very angry microglia, and a continual disruption of the glial limitans,” Dr. Gommerman said. “We were able to see axonal stress in comparison to the young mice. We also saw some evidence of synapse loss. It seems that these animals not only have demyelination in the cortex, but there are problems with the axons and the synapses.”
To apply this model in humans, she and her colleagues collaborated with Netherlands Brain Bank in order to obtain brain samples for analysis with imaging mass cytometry, which provides a time-of-flight mass spectrometry readout of the staining pattern of heavy metal ion–tagged antibodies on a single slide-mounted tissue section.
“We really have to be careful which [brain] samples we choose, because not all samples from progressive MS patients have evidence of meningeal inflammation,” she noted. So far, they have observed that meningeal inflammation is associated with gray matter lesions, rather than with normal-appearing gray matter.
“We also need to look at appropriate controls, so our plan is to look at patients who have meningeal inflammation but do not have MS,” she said.
Dr. Gommerman reported having received grants from Novartis, Roche, and Merck, as well as a consulting agreement with Roche.
EXPERT ANALYSIS FROM ACTRIMS FORUM 2019
MS researchers aim to build MRI diagnostic portfolio beyond the central vein sign
DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
EXPERT ANALYSIS FROM ACTRIMS FORUM 2019