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No teen herd immunity for 4CMenB in landmark trial
LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
REPORTING FROM ESPID 2019
Dapagliflozin meets primary endpoint in the DAPA-HF trial
The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.
DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.
The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.
“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.
Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.
The full results from DAPA-HF will be presented at a later date.
The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.
DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.
The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.
“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.
Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.
The full results from DAPA-HF will be presented at a later date.
The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.
DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.
The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.
“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.
Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.
The full results from DAPA-HF will be presented at a later date.
Adding chemo beats standard gefitinib for EGFR-mutated lung cancer
For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.
Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.
The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m2) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.
After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).
“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.
Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.
Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.
The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.
SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.
For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.
Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.
The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m2) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.
After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).
“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.
Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.
Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.
The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.
SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.
For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.
Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.
The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m2) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.
After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).
“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.
Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.
Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.
The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.
SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Challenges of Treating Primary Psychiatric Disease in Dermatology
Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.1 It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.2 Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.
What primary psychiatric conditions do we see in dermatology?
Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.
Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.3
Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.2 Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.
Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.2 Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.
What treatments are available?
Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.2
Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.4 Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.5-7
Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.2 It addresses maladaptive thought patterns to modify behavior.
Who treats patients with neurodermatoses?
If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.8
Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.9
Should a dermatologist prescribe psychotropic drugs?
In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”10 Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.
Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.9 Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.12
Final Thoughts
The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.
- Korabel H, Dudek D, Jaworek A, et al. Psychodermatology: psychological and psychiatrical aspects of dermatology [in Polish]. Przegl Lek. 2008;65:244-248.
- Krooks JA, Weatherall AG, Holland PJ. Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease. J Dermatolog Treat. 2018;29:418-427.
- Bewley AP, Lepping P, Freundenmann RW, et al. Delusional parasitosis: time to call it delusional infestation. Br J Dermatol. 2018;163:1-2.
- Freudenmann RW, Lepping P. Second-generation antipsychotics in primary and secondary delusional parasitosis: outcome and efficacy. J Clin Psychopharmacol. 2008;28:500-508.
- Miyamoto S, Miyake N, Ogino S, et al. Successful treatment of delusional disorder with low-dose aripiprazole. Psychiatry Clin Neurosci. 2008;62:369.
- Ladizinski B, Busse KL, Bhutani T, et al. Aripiprazole as a viable alternative for treating delusions of parasitosis. J Drugs Dermatol. 2010;9:1531-1532.
- Huang WL, Chang LR. Aripiprazole in the treatment of delusional parasitosis with ocular and dermatologic presentations. J Clin Psychopharmacol. 2013;33:272-273.
- Campbell EH, Elston DM, Hawthorne JD, et al. Diagnosis and management of delusional parasitosis. J Am Acad Dermatol. 2019;80:1428-1434.
- Bhutani T, Lee CS, Koo JYM. Psychotropic agents. In: Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. 3rd ed. China: Elsevier Saunders; 2013:375-388.
- Duncan KO, Koo JYM. Psychocutaneous diseases. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. China: Elsevier; 2018:128-137.
- Shah B, Levenson JL. Use of psychotropic drugs in the dermatology patient: when to start and stop? Clin Dermatol. 2018;36:748-755.
- Gee SN, Zakhary L, Keuthen N, et al. A survey assessment of the recognition and treatment of psychocutaneous disorders in the outpatient dermatology setting: how prepared are we? J Am Acad Dermatol. 2013;68:47-52.
Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.1 It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.2 Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.
What primary psychiatric conditions do we see in dermatology?
Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.
Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.3
Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.2 Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.
Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.2 Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.
What treatments are available?
Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.2
Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.4 Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.5-7
Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.2 It addresses maladaptive thought patterns to modify behavior.
Who treats patients with neurodermatoses?
If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.8
Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.9
Should a dermatologist prescribe psychotropic drugs?
In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”10 Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.
Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.9 Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.12
Final Thoughts
The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.
Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.1 It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.2 Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.
What primary psychiatric conditions do we see in dermatology?
Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.
Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.3
Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.2 Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.
Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.2 Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.
What treatments are available?
Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.2
Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.4 Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.5-7
Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.2 It addresses maladaptive thought patterns to modify behavior.
Who treats patients with neurodermatoses?
If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.8
Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.9
Should a dermatologist prescribe psychotropic drugs?
In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”10 Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.
Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.9 Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.12
Final Thoughts
The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.
- Korabel H, Dudek D, Jaworek A, et al. Psychodermatology: psychological and psychiatrical aspects of dermatology [in Polish]. Przegl Lek. 2008;65:244-248.
- Krooks JA, Weatherall AG, Holland PJ. Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease. J Dermatolog Treat. 2018;29:418-427.
- Bewley AP, Lepping P, Freundenmann RW, et al. Delusional parasitosis: time to call it delusional infestation. Br J Dermatol. 2018;163:1-2.
- Freudenmann RW, Lepping P. Second-generation antipsychotics in primary and secondary delusional parasitosis: outcome and efficacy. J Clin Psychopharmacol. 2008;28:500-508.
- Miyamoto S, Miyake N, Ogino S, et al. Successful treatment of delusional disorder with low-dose aripiprazole. Psychiatry Clin Neurosci. 2008;62:369.
- Ladizinski B, Busse KL, Bhutani T, et al. Aripiprazole as a viable alternative for treating delusions of parasitosis. J Drugs Dermatol. 2010;9:1531-1532.
- Huang WL, Chang LR. Aripiprazole in the treatment of delusional parasitosis with ocular and dermatologic presentations. J Clin Psychopharmacol. 2013;33:272-273.
- Campbell EH, Elston DM, Hawthorne JD, et al. Diagnosis and management of delusional parasitosis. J Am Acad Dermatol. 2019;80:1428-1434.
- Bhutani T, Lee CS, Koo JYM. Psychotropic agents. In: Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. 3rd ed. China: Elsevier Saunders; 2013:375-388.
- Duncan KO, Koo JYM. Psychocutaneous diseases. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. China: Elsevier; 2018:128-137.
- Shah B, Levenson JL. Use of psychotropic drugs in the dermatology patient: when to start and stop? Clin Dermatol. 2018;36:748-755.
- Gee SN, Zakhary L, Keuthen N, et al. A survey assessment of the recognition and treatment of psychocutaneous disorders in the outpatient dermatology setting: how prepared are we? J Am Acad Dermatol. 2013;68:47-52.
- Korabel H, Dudek D, Jaworek A, et al. Psychodermatology: psychological and psychiatrical aspects of dermatology [in Polish]. Przegl Lek. 2008;65:244-248.
- Krooks JA, Weatherall AG, Holland PJ. Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease. J Dermatolog Treat. 2018;29:418-427.
- Bewley AP, Lepping P, Freundenmann RW, et al. Delusional parasitosis: time to call it delusional infestation. Br J Dermatol. 2018;163:1-2.
- Freudenmann RW, Lepping P. Second-generation antipsychotics in primary and secondary delusional parasitosis: outcome and efficacy. J Clin Psychopharmacol. 2008;28:500-508.
- Miyamoto S, Miyake N, Ogino S, et al. Successful treatment of delusional disorder with low-dose aripiprazole. Psychiatry Clin Neurosci. 2008;62:369.
- Ladizinski B, Busse KL, Bhutani T, et al. Aripiprazole as a viable alternative for treating delusions of parasitosis. J Drugs Dermatol. 2010;9:1531-1532.
- Huang WL, Chang LR. Aripiprazole in the treatment of delusional parasitosis with ocular and dermatologic presentations. J Clin Psychopharmacol. 2013;33:272-273.
- Campbell EH, Elston DM, Hawthorne JD, et al. Diagnosis and management of delusional parasitosis. J Am Acad Dermatol. 2019;80:1428-1434.
- Bhutani T, Lee CS, Koo JYM. Psychotropic agents. In: Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. 3rd ed. China: Elsevier Saunders; 2013:375-388.
- Duncan KO, Koo JYM. Psychocutaneous diseases. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. China: Elsevier; 2018:128-137.
- Shah B, Levenson JL. Use of psychotropic drugs in the dermatology patient: when to start and stop? Clin Dermatol. 2018;36:748-755.
- Gee SN, Zakhary L, Keuthen N, et al. A survey assessment of the recognition and treatment of psychocutaneous disorders in the outpatient dermatology setting: how prepared are we? J Am Acad Dermatol. 2013;68:47-52.
Resident Pearl
- Patients often present to dermatology with primary psychologic disorders such as delusional infestation or trichotillomania. Treatment of such conditions with antidepressants and antipsychotics can be highly effective and is within our scope of practice. Increased emphasis on psychopharmacotherapy in dermatology training would increase access to appropriate care for this patient population.
Forging a path for gender equality in medicine
I read with cautious optimism the Diversity Pledge and No–All Male Panel Policy recently announced by the Lancet Group.1 This initiative comes at a crucial time, on the heels of a renewed interest and attention to gender inequities in medicine.
Despite 50-year-old federal legislation mandating that men and women receive equal compensation for equal work, pay inequities persist in all aspects of the workforce and medicine is no exception. In 2018, the American College of Physicians published a position paper acknowledging that, despite an increase in women in the active physician workforce and training positions, our numbers remain disproportionately low in leadership positions, with a mediocre track record for career advancement.2 Inadequate mentorship, discrimination, gender bias, imposter syndrome and a lack of work-life integration have all been cited as contributing to the problem.
Consensus and commitment statements are important first steps in legitimizing a problem, but they do not always engender change. They run the risk of creating an “illusion of fairness” that lulls us into a sense of complacency that change is coming and yet it never does. This is why the Lancet Group’s pledge is so remarkable in its scope. Less than a year after the timely ACP position paper, the Lancet Group published a theme issue addressing the systematic concerns surrounding gender bias in medicine.
Recognizing that publications are prime currency in medicine, the Lancet Group has declared its commitment to increase the representation of women, minorities, and underrepresented geographic areas in editorial boards, peer review, and authorship. Since their #LancetWomen issue, 8 of their 18 journals have refreshed their editorial boards to include at least 50% female membership, with a goal of all 18 journals achieving this landmark by year’s end. That this change is being catapulted by a major publishing group suggests that a necessary cultural transformation is underway.
Today, women are entering the medical field in equal numbers to men. While some may argue that we have achieved gender diversity in medicine, we must not confuse this with gender equity, which remains a distant goal. This is a ripe time in medicine. We have momentum and an opportunity for change.
In an editorial comment to the ACP position paper, Molly Carnes, MD, drew an analogy to the Surgeon General’s report in 1964, which announced that smoking was detrimental to health. The report legitimized the already overwhelming evidence that smoking negatively impacted clinical outcomes and it served as a trigger to propel change.3 Similarly, we hope the ACP position has legitimized the research highlighting gender disparities in medicine and that the Lancet Group’s initiative is among the first of many changes to come.
This change must be embraced and executed by leadership across medical schools, universities, and professional societies. We must collectively pursue interventions and solutions to the multifaceted problem of gender inequity. After all, women have become an integral part of the medical workforce and we all need to work together to ensure both genders have sustainable careers.
Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.
References
1. Lancet. 2019 Aug 10; 394(10197): 452-3.
2. Ann Intern Med. 2018 May 15;168(10):721-3.
3. Ann Intern Med. 2018 May 15;168(10):741-3.
I read with cautious optimism the Diversity Pledge and No–All Male Panel Policy recently announced by the Lancet Group.1 This initiative comes at a crucial time, on the heels of a renewed interest and attention to gender inequities in medicine.
Despite 50-year-old federal legislation mandating that men and women receive equal compensation for equal work, pay inequities persist in all aspects of the workforce and medicine is no exception. In 2018, the American College of Physicians published a position paper acknowledging that, despite an increase in women in the active physician workforce and training positions, our numbers remain disproportionately low in leadership positions, with a mediocre track record for career advancement.2 Inadequate mentorship, discrimination, gender bias, imposter syndrome and a lack of work-life integration have all been cited as contributing to the problem.
Consensus and commitment statements are important first steps in legitimizing a problem, but they do not always engender change. They run the risk of creating an “illusion of fairness” that lulls us into a sense of complacency that change is coming and yet it never does. This is why the Lancet Group’s pledge is so remarkable in its scope. Less than a year after the timely ACP position paper, the Lancet Group published a theme issue addressing the systematic concerns surrounding gender bias in medicine.
Recognizing that publications are prime currency in medicine, the Lancet Group has declared its commitment to increase the representation of women, minorities, and underrepresented geographic areas in editorial boards, peer review, and authorship. Since their #LancetWomen issue, 8 of their 18 journals have refreshed their editorial boards to include at least 50% female membership, with a goal of all 18 journals achieving this landmark by year’s end. That this change is being catapulted by a major publishing group suggests that a necessary cultural transformation is underway.
Today, women are entering the medical field in equal numbers to men. While some may argue that we have achieved gender diversity in medicine, we must not confuse this with gender equity, which remains a distant goal. This is a ripe time in medicine. We have momentum and an opportunity for change.
In an editorial comment to the ACP position paper, Molly Carnes, MD, drew an analogy to the Surgeon General’s report in 1964, which announced that smoking was detrimental to health. The report legitimized the already overwhelming evidence that smoking negatively impacted clinical outcomes and it served as a trigger to propel change.3 Similarly, we hope the ACP position has legitimized the research highlighting gender disparities in medicine and that the Lancet Group’s initiative is among the first of many changes to come.
This change must be embraced and executed by leadership across medical schools, universities, and professional societies. We must collectively pursue interventions and solutions to the multifaceted problem of gender inequity. After all, women have become an integral part of the medical workforce and we all need to work together to ensure both genders have sustainable careers.
Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.
References
1. Lancet. 2019 Aug 10; 394(10197): 452-3.
2. Ann Intern Med. 2018 May 15;168(10):721-3.
3. Ann Intern Med. 2018 May 15;168(10):741-3.
I read with cautious optimism the Diversity Pledge and No–All Male Panel Policy recently announced by the Lancet Group.1 This initiative comes at a crucial time, on the heels of a renewed interest and attention to gender inequities in medicine.
Despite 50-year-old federal legislation mandating that men and women receive equal compensation for equal work, pay inequities persist in all aspects of the workforce and medicine is no exception. In 2018, the American College of Physicians published a position paper acknowledging that, despite an increase in women in the active physician workforce and training positions, our numbers remain disproportionately low in leadership positions, with a mediocre track record for career advancement.2 Inadequate mentorship, discrimination, gender bias, imposter syndrome and a lack of work-life integration have all been cited as contributing to the problem.
Consensus and commitment statements are important first steps in legitimizing a problem, but they do not always engender change. They run the risk of creating an “illusion of fairness” that lulls us into a sense of complacency that change is coming and yet it never does. This is why the Lancet Group’s pledge is so remarkable in its scope. Less than a year after the timely ACP position paper, the Lancet Group published a theme issue addressing the systematic concerns surrounding gender bias in medicine.
Recognizing that publications are prime currency in medicine, the Lancet Group has declared its commitment to increase the representation of women, minorities, and underrepresented geographic areas in editorial boards, peer review, and authorship. Since their #LancetWomen issue, 8 of their 18 journals have refreshed their editorial boards to include at least 50% female membership, with a goal of all 18 journals achieving this landmark by year’s end. That this change is being catapulted by a major publishing group suggests that a necessary cultural transformation is underway.
Today, women are entering the medical field in equal numbers to men. While some may argue that we have achieved gender diversity in medicine, we must not confuse this with gender equity, which remains a distant goal. This is a ripe time in medicine. We have momentum and an opportunity for change.
In an editorial comment to the ACP position paper, Molly Carnes, MD, drew an analogy to the Surgeon General’s report in 1964, which announced that smoking was detrimental to health. The report legitimized the already overwhelming evidence that smoking negatively impacted clinical outcomes and it served as a trigger to propel change.3 Similarly, we hope the ACP position has legitimized the research highlighting gender disparities in medicine and that the Lancet Group’s initiative is among the first of many changes to come.
This change must be embraced and executed by leadership across medical schools, universities, and professional societies. We must collectively pursue interventions and solutions to the multifaceted problem of gender inequity. After all, women have become an integral part of the medical workforce and we all need to work together to ensure both genders have sustainable careers.
Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.
References
1. Lancet. 2019 Aug 10; 394(10197): 452-3.
2. Ann Intern Med. 2018 May 15;168(10):721-3.
3. Ann Intern Med. 2018 May 15;168(10):741-3.
Cancer survivors face more age-related deficits
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
FROM CANCER
HCV coinfection adds to cardiovascular risk in HIV-infected patients
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
FROM ANTIVIRAL RESEARCH
Obinutuzumab-lenalidomide combo shows promise in relapsed/refractory FL
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
FROM THE LANCET HAEMATOLOGY
False links between violence, mental illness fast-tracked report release
Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.
“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.
The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.
Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.
According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”
, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.
“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.
More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.
The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.
Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.
Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.
The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.
Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.
“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.
Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.
In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.
The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.
Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.
“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.
The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.
Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.
According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”
, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.
“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.
More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.
The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.
Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.
Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.
The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.
Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.
“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.
Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.
In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.
The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.
Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.
“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.
The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.
Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.
According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”
, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.
“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.
More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.
The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.
Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.
Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.
The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.
Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.
“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.
Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.
In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.
The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.
Diabetes effect in heart failure varies by phenotype
Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.
Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden
Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.
For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.
The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.
Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.
The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.
Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.
Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.
Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden
Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.
For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.
The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.
Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.
The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.
Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.
Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.
Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden
Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.
For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.
The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.
Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.
The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.
Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point: Patients with heart failure and type 2 diabetes have smaller left ventricular ejection fractions, poorer quality of life, and increased risk for all-cause and cardiovascular death and hospitalization for heart failure.
Major finding: Heart failure with comorbid type 2 diabetes is associated with cardiac remodeling, worse clinical outcomes, and higher risk for hospitalization; type of heart failure may have a role.
Study details: A prospective, multicenter cohort of 6,167 patients with heart failure in the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry enrolled in 11 Asian countries and 965 community-based controls without heart failure recruited as part of the control arm of the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study.
Disclosures: The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.
Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.