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Major survey spotlights novel factors influencing acne
MADRID – Do you ask your acne patients if they use cannabis? And if they say yes, do you suggest they consider giving it up? Dermatologist Delphine Kerob, MD, believes you should.
In a late-breaker session at the annual congress of the European Academy of Dermatology and Venereology, she presented . One of the biggest surprises in this first-of-its-kind study was the finding of an association between cannabis use and acne: 21.1% of patients with physician-diagnosed acne were users, compared with 16.6% of controls without acne.
“I think as dermatologists we should ask these kinds of questions when we manage our patients because this may influence the course of their acne,” observed Dr. Kerob, who is the international medical director for Vichy Laboratories in Paris. The survey was sponsored by the company.
This was an Internet-based survey of 2,826 acne patients and 3,853 age- and sex-matched controls without acne. It was conducted in Canada, France, Germany, Italy, Brazil, and Russia.
The survey comprehensively addressed for the first time what lead investigator Brigitte Dreno, MD, PhD, professor and head of dermatology at Nantes (France) University Hospital and EADV Scientific Programming Committee Chair, has previously called the “acne exposome.” The exposome is essentially everything in a patient’s external and internal environment – other than genetics – that influences the occurrence and severity of the disease (J Eur Acad Dermatol Venereol. 2018 May;32[5]:812-9).
The survey probed the six major categories of exposome factors as defined by Dr. Dreno and coauthors: nutrition, air pollution, lifestyle and psychological factors, medications, skin care products, and climate. Here are the highlights:
Lifestyle and psychological factors. While cannabis use emerged as a novel factor linked to increased likelihood of acne, tobacco use was not – a surprising finding because other investigators had previously identified it as an acne trigger.
Feeling burdened by psychological stress was reported by 51% of acne patients and 29% of controls, for an adjusted 1.79-fold increased risk of acne.
Air pollution. Acne patients were significantly more likely to report exposure to solvent vapors, crude oil, tars, frying oil vapors, and living near an airport or close to factories with chimneys. Dr. Kerob noted that these findings are consistent with other investigators’ study of 189 residents of heavily polluted Mexico City or more pristine Cuernavaca, Mexico, with less pollution. The Mexico City cohort demonstrated an increased sebum excretion rate, lower levels of the antioxidants vitamin E and squalene in their sebum, and a less cohesive stratum corneum, along with a higher prevalence of atopic skin and facial seborrheic changes (Int J Cosmet Sci. 2015 Jun;37[3]:329-38).
Nutrition. This is a hot topic that acne patients have many questions about. Myths abound, as detailed by an expert panel including Dr. Dreno in an article entitled, “Acne and Nutrition: Hypotheses, Myths and Facts” (J Eur Acad Dermatol Venereol. 2018 Oct;32[10]:1631-7).
Dr. Kerob reported that the survey showed consumption of dairy products, probiotics, chocolate, cakes and other sweets, soft drinks, fruit juice, and whey protein were each associated with a significantly increased likelihood of acne .
Fifty-seven percent of acne patients indicated they consumed high-alcohol distilled spirits, compared with 43% of controls.
“We know that on our sebaceous glands, as well as on keratinocytes, we have receptors that will be activated by the impact of some nutrients,” she commented.
Among these receptors on sebaceous glands are the insulin growth factor–1 receptor, the leptin receptor, histamine receptors, receptors for substance P, peroxisome proliferator-activated receptors alpha, beta, and gamma, and androgen receptors, she added.
Medications. For Dr. Kerob, another surprise study finding was that 11.9% of acne patients had used an anabolic steroid- or testosterone-based hormonal drug within the previous 12 months, compared with 3.2% of controls without acne.
Cosmetic factors. The use of facial scrubs, harsh cleansers, and dermarollers was significantly more common among the acne patients.
Climate. Acne patients were more likely to live in hot and/or humid locations. For example, 24.6% of the acne group lived in a hot climate, versus 17.1% of controls.
“We think that identifying and reducing the impact of the exposome is very important for an adequate and holistic acne disease management,” the researcher concluded.
However, Eric Simpson, MD, rose from the audience to comment that he finds this plethora of associations to be of little use in advising his acne patients in clinical practice. For example, does cannabis use cause acne, or are acne patients more likely to be cannabis users as a means of coping with the social stigma surrounding their skin disease?
“I’d just caution about confounding association with causation. Let’s look at trials of removing that association to see if it actually improves acne before we make strong recommendations in the clinic,” urged Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.
“You’re perfectly right, there,” Dr. Kerob replied. “The methodology of our study can’t separate cause from effect. But as dermatologists, if we have patients with acne that’s resistant to treatment, we need to see if there are other factors that could worsen acne outcome. And we have patients asking us questions all the time about nutrition – now we have some answers that we can provide to those patients.”
The study was sponsored by Vichy Laboratories, and Dr. Kerob is an employee of the company.
MADRID – Do you ask your acne patients if they use cannabis? And if they say yes, do you suggest they consider giving it up? Dermatologist Delphine Kerob, MD, believes you should.
In a late-breaker session at the annual congress of the European Academy of Dermatology and Venereology, she presented . One of the biggest surprises in this first-of-its-kind study was the finding of an association between cannabis use and acne: 21.1% of patients with physician-diagnosed acne were users, compared with 16.6% of controls without acne.
“I think as dermatologists we should ask these kinds of questions when we manage our patients because this may influence the course of their acne,” observed Dr. Kerob, who is the international medical director for Vichy Laboratories in Paris. The survey was sponsored by the company.
This was an Internet-based survey of 2,826 acne patients and 3,853 age- and sex-matched controls without acne. It was conducted in Canada, France, Germany, Italy, Brazil, and Russia.
The survey comprehensively addressed for the first time what lead investigator Brigitte Dreno, MD, PhD, professor and head of dermatology at Nantes (France) University Hospital and EADV Scientific Programming Committee Chair, has previously called the “acne exposome.” The exposome is essentially everything in a patient’s external and internal environment – other than genetics – that influences the occurrence and severity of the disease (J Eur Acad Dermatol Venereol. 2018 May;32[5]:812-9).
The survey probed the six major categories of exposome factors as defined by Dr. Dreno and coauthors: nutrition, air pollution, lifestyle and psychological factors, medications, skin care products, and climate. Here are the highlights:
Lifestyle and psychological factors. While cannabis use emerged as a novel factor linked to increased likelihood of acne, tobacco use was not – a surprising finding because other investigators had previously identified it as an acne trigger.
Feeling burdened by psychological stress was reported by 51% of acne patients and 29% of controls, for an adjusted 1.79-fold increased risk of acne.
Air pollution. Acne patients were significantly more likely to report exposure to solvent vapors, crude oil, tars, frying oil vapors, and living near an airport or close to factories with chimneys. Dr. Kerob noted that these findings are consistent with other investigators’ study of 189 residents of heavily polluted Mexico City or more pristine Cuernavaca, Mexico, with less pollution. The Mexico City cohort demonstrated an increased sebum excretion rate, lower levels of the antioxidants vitamin E and squalene in their sebum, and a less cohesive stratum corneum, along with a higher prevalence of atopic skin and facial seborrheic changes (Int J Cosmet Sci. 2015 Jun;37[3]:329-38).
Nutrition. This is a hot topic that acne patients have many questions about. Myths abound, as detailed by an expert panel including Dr. Dreno in an article entitled, “Acne and Nutrition: Hypotheses, Myths and Facts” (J Eur Acad Dermatol Venereol. 2018 Oct;32[10]:1631-7).
Dr. Kerob reported that the survey showed consumption of dairy products, probiotics, chocolate, cakes and other sweets, soft drinks, fruit juice, and whey protein were each associated with a significantly increased likelihood of acne .
Fifty-seven percent of acne patients indicated they consumed high-alcohol distilled spirits, compared with 43% of controls.
“We know that on our sebaceous glands, as well as on keratinocytes, we have receptors that will be activated by the impact of some nutrients,” she commented.
Among these receptors on sebaceous glands are the insulin growth factor–1 receptor, the leptin receptor, histamine receptors, receptors for substance P, peroxisome proliferator-activated receptors alpha, beta, and gamma, and androgen receptors, she added.
Medications. For Dr. Kerob, another surprise study finding was that 11.9% of acne patients had used an anabolic steroid- or testosterone-based hormonal drug within the previous 12 months, compared with 3.2% of controls without acne.
Cosmetic factors. The use of facial scrubs, harsh cleansers, and dermarollers was significantly more common among the acne patients.
Climate. Acne patients were more likely to live in hot and/or humid locations. For example, 24.6% of the acne group lived in a hot climate, versus 17.1% of controls.
“We think that identifying and reducing the impact of the exposome is very important for an adequate and holistic acne disease management,” the researcher concluded.
However, Eric Simpson, MD, rose from the audience to comment that he finds this plethora of associations to be of little use in advising his acne patients in clinical practice. For example, does cannabis use cause acne, or are acne patients more likely to be cannabis users as a means of coping with the social stigma surrounding their skin disease?
“I’d just caution about confounding association with causation. Let’s look at trials of removing that association to see if it actually improves acne before we make strong recommendations in the clinic,” urged Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.
“You’re perfectly right, there,” Dr. Kerob replied. “The methodology of our study can’t separate cause from effect. But as dermatologists, if we have patients with acne that’s resistant to treatment, we need to see if there are other factors that could worsen acne outcome. And we have patients asking us questions all the time about nutrition – now we have some answers that we can provide to those patients.”
The study was sponsored by Vichy Laboratories, and Dr. Kerob is an employee of the company.
MADRID – Do you ask your acne patients if they use cannabis? And if they say yes, do you suggest they consider giving it up? Dermatologist Delphine Kerob, MD, believes you should.
In a late-breaker session at the annual congress of the European Academy of Dermatology and Venereology, she presented . One of the biggest surprises in this first-of-its-kind study was the finding of an association between cannabis use and acne: 21.1% of patients with physician-diagnosed acne were users, compared with 16.6% of controls without acne.
“I think as dermatologists we should ask these kinds of questions when we manage our patients because this may influence the course of their acne,” observed Dr. Kerob, who is the international medical director for Vichy Laboratories in Paris. The survey was sponsored by the company.
This was an Internet-based survey of 2,826 acne patients and 3,853 age- and sex-matched controls without acne. It was conducted in Canada, France, Germany, Italy, Brazil, and Russia.
The survey comprehensively addressed for the first time what lead investigator Brigitte Dreno, MD, PhD, professor and head of dermatology at Nantes (France) University Hospital and EADV Scientific Programming Committee Chair, has previously called the “acne exposome.” The exposome is essentially everything in a patient’s external and internal environment – other than genetics – that influences the occurrence and severity of the disease (J Eur Acad Dermatol Venereol. 2018 May;32[5]:812-9).
The survey probed the six major categories of exposome factors as defined by Dr. Dreno and coauthors: nutrition, air pollution, lifestyle and psychological factors, medications, skin care products, and climate. Here are the highlights:
Lifestyle and psychological factors. While cannabis use emerged as a novel factor linked to increased likelihood of acne, tobacco use was not – a surprising finding because other investigators had previously identified it as an acne trigger.
Feeling burdened by psychological stress was reported by 51% of acne patients and 29% of controls, for an adjusted 1.79-fold increased risk of acne.
Air pollution. Acne patients were significantly more likely to report exposure to solvent vapors, crude oil, tars, frying oil vapors, and living near an airport or close to factories with chimneys. Dr. Kerob noted that these findings are consistent with other investigators’ study of 189 residents of heavily polluted Mexico City or more pristine Cuernavaca, Mexico, with less pollution. The Mexico City cohort demonstrated an increased sebum excretion rate, lower levels of the antioxidants vitamin E and squalene in their sebum, and a less cohesive stratum corneum, along with a higher prevalence of atopic skin and facial seborrheic changes (Int J Cosmet Sci. 2015 Jun;37[3]:329-38).
Nutrition. This is a hot topic that acne patients have many questions about. Myths abound, as detailed by an expert panel including Dr. Dreno in an article entitled, “Acne and Nutrition: Hypotheses, Myths and Facts” (J Eur Acad Dermatol Venereol. 2018 Oct;32[10]:1631-7).
Dr. Kerob reported that the survey showed consumption of dairy products, probiotics, chocolate, cakes and other sweets, soft drinks, fruit juice, and whey protein were each associated with a significantly increased likelihood of acne .
Fifty-seven percent of acne patients indicated they consumed high-alcohol distilled spirits, compared with 43% of controls.
“We know that on our sebaceous glands, as well as on keratinocytes, we have receptors that will be activated by the impact of some nutrients,” she commented.
Among these receptors on sebaceous glands are the insulin growth factor–1 receptor, the leptin receptor, histamine receptors, receptors for substance P, peroxisome proliferator-activated receptors alpha, beta, and gamma, and androgen receptors, she added.
Medications. For Dr. Kerob, another surprise study finding was that 11.9% of acne patients had used an anabolic steroid- or testosterone-based hormonal drug within the previous 12 months, compared with 3.2% of controls without acne.
Cosmetic factors. The use of facial scrubs, harsh cleansers, and dermarollers was significantly more common among the acne patients.
Climate. Acne patients were more likely to live in hot and/or humid locations. For example, 24.6% of the acne group lived in a hot climate, versus 17.1% of controls.
“We think that identifying and reducing the impact of the exposome is very important for an adequate and holistic acne disease management,” the researcher concluded.
However, Eric Simpson, MD, rose from the audience to comment that he finds this plethora of associations to be of little use in advising his acne patients in clinical practice. For example, does cannabis use cause acne, or are acne patients more likely to be cannabis users as a means of coping with the social stigma surrounding their skin disease?
“I’d just caution about confounding association with causation. Let’s look at trials of removing that association to see if it actually improves acne before we make strong recommendations in the clinic,” urged Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.
“You’re perfectly right, there,” Dr. Kerob replied. “The methodology of our study can’t separate cause from effect. But as dermatologists, if we have patients with acne that’s resistant to treatment, we need to see if there are other factors that could worsen acne outcome. And we have patients asking us questions all the time about nutrition – now we have some answers that we can provide to those patients.”
The study was sponsored by Vichy Laboratories, and Dr. Kerob is an employee of the company.
REPORTING FROM EADV 2019
Lazertinib has good showing in EGFR-mutated advanced NSCLC
Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.
Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.
Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.
“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.
“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.
The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.
Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).
Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.
On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.
The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).
Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.
Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.
SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.
“[W]hy should anyone care about all these data for lazertinib?” Tejas Patil, MD, and D. Ross Camidge, MD, PhD, asked in a commentary, noting that another third-generation EGFR TKI, osimertinib (Tagrisso), has already received Food and Drug Administration approval for use in this setting and has generally similar activity and tolerability.
“Beyond any potential competitive price advantage that could be introduced after licensing, or idiosyncratic tolerance of one drug over another in individual patients, the real potential advantage of lazertinib might be hiding in plain sight. Specifically, lazertinib’s incompletely explored potential to treat CNS metastases,” they noted.
Although osimertinib appears to have good CNS activity, patients with CNS metastases continue to experience poorer progression-free survival. And even at higher doses causing greater toxicity, CNS penetration of that drug is limited.
“[T]he ideal drug for dedicated CNS dose regimen exploration is one in which the standard dosing has been set in the absence of substantial toxicity and in the absence of any plateauing of pharmacokinetic exposures,” Dr. Patil and Dr. Camidge maintained. And lazertinib appears to fit that bill.
The 44% intracranial response rate “is encouraging but still leaves a substantial amount of important data to be generated,” they contended. Although progression in the CNS was uncommon among patients without CNS metastases at baseline, the longer median progression-free survival at higher doses may indicate better CNS control and support further dose escalation.
“Lazertinib could be one of the pioneer drugs for redefining how we optimally address the CNS in oncology drug development,” they concluded. “Taking full advantage of the early drug-development process to explore the CNS potential of any oncology drug being considered in disease types with a high rate of CNS metastases should be part of a future that we can all look forward to.”
Dr. Patil is instructor of medicine, and Dr. Camidge is professor of medicine, in the division of medical oncology, department of medicine, at the University of Colorado, Anschutz Medical Campus, Aurora.
“[W]hy should anyone care about all these data for lazertinib?” Tejas Patil, MD, and D. Ross Camidge, MD, PhD, asked in a commentary, noting that another third-generation EGFR TKI, osimertinib (Tagrisso), has already received Food and Drug Administration approval for use in this setting and has generally similar activity and tolerability.
“Beyond any potential competitive price advantage that could be introduced after licensing, or idiosyncratic tolerance of one drug over another in individual patients, the real potential advantage of lazertinib might be hiding in plain sight. Specifically, lazertinib’s incompletely explored potential to treat CNS metastases,” they noted.
Although osimertinib appears to have good CNS activity, patients with CNS metastases continue to experience poorer progression-free survival. And even at higher doses causing greater toxicity, CNS penetration of that drug is limited.
“[T]he ideal drug for dedicated CNS dose regimen exploration is one in which the standard dosing has been set in the absence of substantial toxicity and in the absence of any plateauing of pharmacokinetic exposures,” Dr. Patil and Dr. Camidge maintained. And lazertinib appears to fit that bill.
The 44% intracranial response rate “is encouraging but still leaves a substantial amount of important data to be generated,” they contended. Although progression in the CNS was uncommon among patients without CNS metastases at baseline, the longer median progression-free survival at higher doses may indicate better CNS control and support further dose escalation.
“Lazertinib could be one of the pioneer drugs for redefining how we optimally address the CNS in oncology drug development,” they concluded. “Taking full advantage of the early drug-development process to explore the CNS potential of any oncology drug being considered in disease types with a high rate of CNS metastases should be part of a future that we can all look forward to.”
Dr. Patil is instructor of medicine, and Dr. Camidge is professor of medicine, in the division of medical oncology, department of medicine, at the University of Colorado, Anschutz Medical Campus, Aurora.
“[W]hy should anyone care about all these data for lazertinib?” Tejas Patil, MD, and D. Ross Camidge, MD, PhD, asked in a commentary, noting that another third-generation EGFR TKI, osimertinib (Tagrisso), has already received Food and Drug Administration approval for use in this setting and has generally similar activity and tolerability.
“Beyond any potential competitive price advantage that could be introduced after licensing, or idiosyncratic tolerance of one drug over another in individual patients, the real potential advantage of lazertinib might be hiding in plain sight. Specifically, lazertinib’s incompletely explored potential to treat CNS metastases,” they noted.
Although osimertinib appears to have good CNS activity, patients with CNS metastases continue to experience poorer progression-free survival. And even at higher doses causing greater toxicity, CNS penetration of that drug is limited.
“[T]he ideal drug for dedicated CNS dose regimen exploration is one in which the standard dosing has been set in the absence of substantial toxicity and in the absence of any plateauing of pharmacokinetic exposures,” Dr. Patil and Dr. Camidge maintained. And lazertinib appears to fit that bill.
The 44% intracranial response rate “is encouraging but still leaves a substantial amount of important data to be generated,” they contended. Although progression in the CNS was uncommon among patients without CNS metastases at baseline, the longer median progression-free survival at higher doses may indicate better CNS control and support further dose escalation.
“Lazertinib could be one of the pioneer drugs for redefining how we optimally address the CNS in oncology drug development,” they concluded. “Taking full advantage of the early drug-development process to explore the CNS potential of any oncology drug being considered in disease types with a high rate of CNS metastases should be part of a future that we can all look forward to.”
Dr. Patil is instructor of medicine, and Dr. Camidge is professor of medicine, in the division of medical oncology, department of medicine, at the University of Colorado, Anschutz Medical Campus, Aurora.
Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.
Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.
Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.
“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.
“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.
The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.
Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).
Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.
On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.
The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).
Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.
Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.
SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.
Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.
Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.
Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.
“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.
“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.
The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.
Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).
Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.
On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.
The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).
Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.
Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.
SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.
FROM LANCET ONCOLOGY
No tacrolimus/cancer link in atopic dermatitis in 10-year study
MADRID – participating in the large, prospective, observational APPLES study, Regina Folster-Holst, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
With nearly 45,000 person-years of follow-up in APPLES (A Prospective Pediatric Longitudinal Evaluation Study), there were no lymphomas and just a single case of skin cancer. That’s highly reassuring, since those were the two types of malignancies singled out as being of particular concern in the boxed warnings for the topical calcineurin inhibitors tacrolimus and pimecrolimus mandated by U.S. and European regulatory agencies in 2005, noted Dr. Folster-Holst, professor of dermatology at Christian Albrechts University of Kiel (Germany).
APPLES included 7,954 children with moderate or severe AD who were a median of 6 years old at enrollment in the study, conducted at 314 sites in the United States, Canada, and seven European countries. This was a naturalistic study in which patients used the topical calcineurin inhibitor as needed, with no restrictions.
A total of six cancers were diagnosed in six individuals during 44,629 person-years of prospective follow-up: one case each of chronic myeloid leukemia, alveolar rhabdomyosarcoma, malignant paraganglioma, carcinoid tumor of the appendix, spinal cord neoplasm, and Spitzoid melanoma. None of those malignancies are classically associated with immunosuppressive therapy.
The primary outcome in APPLES was the standardized incidence ratio of observed cancers to the expected number based upon extrapolation from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, as well as national cancer registries in the other countries where the study was carried out. The expected number of cancers was 5.95, yielding a standardized incidence ratio of 1.01.
Only 27% of patients completed the study. Investigators had anticipated a substantial attrition rate and recalculated their statistics based upon a range of hypothetically increased cancer rates among the dropouts. Even if the cancer rate was 2.5-fold higher in dropouts than in those who remained in the study – a far-fetched possibility – the standardized incidence ratio would not be significantly affected, according to Dr. Folster-Holst.
The new APPLES findings were preceded by a favorable report on long-term use of topical pimecrolimus from the Pediatric Eczema Elective Registry (PEER). The study included 7,457 pimecrolimus-using children with AD followed for 26,792 person-years. The standardized incidence ratio for all cancers was not significantly increased at 1.2. The investigators concluded “it seems unlikely” that topical pimecrolimus as generally used for treatment of AD is associated with an increased risk of malignancy (JAMA Dermatol. 2015 Jun;151[6]:594-9).
The boxed warnings for the topical calcineurin inhibitors have been the source of enormous frustration for dermatologists. The warnings were ordered because of regulatory concern about an increased risk of malignancy in organ transplant recipients on systemic calcineurin inhibitors for immunosuppression, even though the topical agents – unlike the systemic versions – are used intermittently, their systemic absorption is low to nil, and no plausible mechanism by which they could cause cancer has been put forth. Many physicians believe these drugs are probably safer than topical corticosteroids, so the first question put to Dr. Folster-Holst from the audience was, When will the boxed warnings be removed?
“That’s a good question,” she replied. “Patients and parents are afraid. But I think we have now a good argument to move forward with topically applied calcineurin inhibitors.”
Dr. Folster-Holst reported having no financial conflicts of interest regarding the APPLES study, funded by LEO Pharma.
MADRID – participating in the large, prospective, observational APPLES study, Regina Folster-Holst, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
With nearly 45,000 person-years of follow-up in APPLES (A Prospective Pediatric Longitudinal Evaluation Study), there were no lymphomas and just a single case of skin cancer. That’s highly reassuring, since those were the two types of malignancies singled out as being of particular concern in the boxed warnings for the topical calcineurin inhibitors tacrolimus and pimecrolimus mandated by U.S. and European regulatory agencies in 2005, noted Dr. Folster-Holst, professor of dermatology at Christian Albrechts University of Kiel (Germany).
APPLES included 7,954 children with moderate or severe AD who were a median of 6 years old at enrollment in the study, conducted at 314 sites in the United States, Canada, and seven European countries. This was a naturalistic study in which patients used the topical calcineurin inhibitor as needed, with no restrictions.
A total of six cancers were diagnosed in six individuals during 44,629 person-years of prospective follow-up: one case each of chronic myeloid leukemia, alveolar rhabdomyosarcoma, malignant paraganglioma, carcinoid tumor of the appendix, spinal cord neoplasm, and Spitzoid melanoma. None of those malignancies are classically associated with immunosuppressive therapy.
The primary outcome in APPLES was the standardized incidence ratio of observed cancers to the expected number based upon extrapolation from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, as well as national cancer registries in the other countries where the study was carried out. The expected number of cancers was 5.95, yielding a standardized incidence ratio of 1.01.
Only 27% of patients completed the study. Investigators had anticipated a substantial attrition rate and recalculated their statistics based upon a range of hypothetically increased cancer rates among the dropouts. Even if the cancer rate was 2.5-fold higher in dropouts than in those who remained in the study – a far-fetched possibility – the standardized incidence ratio would not be significantly affected, according to Dr. Folster-Holst.
The new APPLES findings were preceded by a favorable report on long-term use of topical pimecrolimus from the Pediatric Eczema Elective Registry (PEER). The study included 7,457 pimecrolimus-using children with AD followed for 26,792 person-years. The standardized incidence ratio for all cancers was not significantly increased at 1.2. The investigators concluded “it seems unlikely” that topical pimecrolimus as generally used for treatment of AD is associated with an increased risk of malignancy (JAMA Dermatol. 2015 Jun;151[6]:594-9).
The boxed warnings for the topical calcineurin inhibitors have been the source of enormous frustration for dermatologists. The warnings were ordered because of regulatory concern about an increased risk of malignancy in organ transplant recipients on systemic calcineurin inhibitors for immunosuppression, even though the topical agents – unlike the systemic versions – are used intermittently, their systemic absorption is low to nil, and no plausible mechanism by which they could cause cancer has been put forth. Many physicians believe these drugs are probably safer than topical corticosteroids, so the first question put to Dr. Folster-Holst from the audience was, When will the boxed warnings be removed?
“That’s a good question,” she replied. “Patients and parents are afraid. But I think we have now a good argument to move forward with topically applied calcineurin inhibitors.”
Dr. Folster-Holst reported having no financial conflicts of interest regarding the APPLES study, funded by LEO Pharma.
MADRID – participating in the large, prospective, observational APPLES study, Regina Folster-Holst, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
With nearly 45,000 person-years of follow-up in APPLES (A Prospective Pediatric Longitudinal Evaluation Study), there were no lymphomas and just a single case of skin cancer. That’s highly reassuring, since those were the two types of malignancies singled out as being of particular concern in the boxed warnings for the topical calcineurin inhibitors tacrolimus and pimecrolimus mandated by U.S. and European regulatory agencies in 2005, noted Dr. Folster-Holst, professor of dermatology at Christian Albrechts University of Kiel (Germany).
APPLES included 7,954 children with moderate or severe AD who were a median of 6 years old at enrollment in the study, conducted at 314 sites in the United States, Canada, and seven European countries. This was a naturalistic study in which patients used the topical calcineurin inhibitor as needed, with no restrictions.
A total of six cancers were diagnosed in six individuals during 44,629 person-years of prospective follow-up: one case each of chronic myeloid leukemia, alveolar rhabdomyosarcoma, malignant paraganglioma, carcinoid tumor of the appendix, spinal cord neoplasm, and Spitzoid melanoma. None of those malignancies are classically associated with immunosuppressive therapy.
The primary outcome in APPLES was the standardized incidence ratio of observed cancers to the expected number based upon extrapolation from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, as well as national cancer registries in the other countries where the study was carried out. The expected number of cancers was 5.95, yielding a standardized incidence ratio of 1.01.
Only 27% of patients completed the study. Investigators had anticipated a substantial attrition rate and recalculated their statistics based upon a range of hypothetically increased cancer rates among the dropouts. Even if the cancer rate was 2.5-fold higher in dropouts than in those who remained in the study – a far-fetched possibility – the standardized incidence ratio would not be significantly affected, according to Dr. Folster-Holst.
The new APPLES findings were preceded by a favorable report on long-term use of topical pimecrolimus from the Pediatric Eczema Elective Registry (PEER). The study included 7,457 pimecrolimus-using children with AD followed for 26,792 person-years. The standardized incidence ratio for all cancers was not significantly increased at 1.2. The investigators concluded “it seems unlikely” that topical pimecrolimus as generally used for treatment of AD is associated with an increased risk of malignancy (JAMA Dermatol. 2015 Jun;151[6]:594-9).
The boxed warnings for the topical calcineurin inhibitors have been the source of enormous frustration for dermatologists. The warnings were ordered because of regulatory concern about an increased risk of malignancy in organ transplant recipients on systemic calcineurin inhibitors for immunosuppression, even though the topical agents – unlike the systemic versions – are used intermittently, their systemic absorption is low to nil, and no plausible mechanism by which they could cause cancer has been put forth. Many physicians believe these drugs are probably safer than topical corticosteroids, so the first question put to Dr. Folster-Holst from the audience was, When will the boxed warnings be removed?
“That’s a good question,” she replied. “Patients and parents are afraid. But I think we have now a good argument to move forward with topically applied calcineurin inhibitors.”
Dr. Folster-Holst reported having no financial conflicts of interest regarding the APPLES study, funded by LEO Pharma.
REPORTING FROM THE EADV CONGRESS
Treating comorbid ADHD-SUD presents challenges
Consider medications that might improve both conditions
SAN DIEGO – Research suggests that as many as 23% of patients with substance use disorder (SUD) also have ADHD, adding an extra layer of complexity to a difficult-to-treat condition. What to do?
“Treating the ADHD can be useful in reducing the severity of symptoms without worsening the substance use disorder. It shouldn’t be avoided,” said psychiatrist Larissa J. Mooney, MD, of the University of California, Los Angeles, and the Veterans Affairs Greater Los Angeles Healthcare System, in a presentation at the annual Psych Congress.
When ADHD is on board, “it’s a more complicated and challenging clinical course,” Dr. Mooney said. The duo of disorders is linked to higher rates of polysubstance abuse and other psychiatric conditions, such as anxiety, bipolar disorder, posttraumatic stress, and antisocial/borderline conditions (Eur Addict Res. 2018;24[1]:43-51).
“These individuals typically have more difficulty with [drug] abstinence, more health consequences, and reduced quality of life, and social and professional consequences,” she said. “Some studies have suggested that they may not respond to lower doses of medication for attention-deficit/hyperactivity disorder and may require doses in the higher range.”
Research has hinted that several drugs that might prove helpful in these patients by improving both conditions, Dr. Mooney said. These include up to 180 mg/day of methylphenidate (Ritalin), 60- and 80-mg doses of mixed amphetamine salts/extended release, atomoxetine (Strattera), and bupropion.
In regard to bupropion, she said, “I find it to be a good choice in my substance use disorder patients for their depression and concentration problems. I have a greater number of individuals at 450 milligrams per day and the XL formulation.”
“We need more research to show if this is helpful,” she said. “It’s a reasonable choice in terms of weighing pros and cons, because it’s not [a controlled substance].”
Still, some of those medications are stimulants, Dr. Mooney said, and their use in patients with SUD is controversial. There are concerns about misuse and diversion.
“We want to have some flexibility,” she said, but it’s important to think about risks and priorities. In certain cases, ADHD may be a secondary concern.
“Some patients have a severe substance use disorder that keeps landing them in the emergency room or causing them to be hospitalized,” she said. “I’m more worried about that than the impairment function from ADHD.”
If you do consider stimulants, she said, longer-acting formulations can be less risky because there’s less potential for diversion. “Also, think about their treatment plan: Is their functioning improving? Are they or showing up for appointments? These are factors that will say: ‘Oh, I’m on the right path with this medication.’ ”
Behavioral treatment also can be helpful in these patients, she said, although “some may not be willing or motivated to put in the time that it takes to do the behavioral work.”
Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.
Consider medications that might improve both conditions
Consider medications that might improve both conditions
SAN DIEGO – Research suggests that as many as 23% of patients with substance use disorder (SUD) also have ADHD, adding an extra layer of complexity to a difficult-to-treat condition. What to do?
“Treating the ADHD can be useful in reducing the severity of symptoms without worsening the substance use disorder. It shouldn’t be avoided,” said psychiatrist Larissa J. Mooney, MD, of the University of California, Los Angeles, and the Veterans Affairs Greater Los Angeles Healthcare System, in a presentation at the annual Psych Congress.
When ADHD is on board, “it’s a more complicated and challenging clinical course,” Dr. Mooney said. The duo of disorders is linked to higher rates of polysubstance abuse and other psychiatric conditions, such as anxiety, bipolar disorder, posttraumatic stress, and antisocial/borderline conditions (Eur Addict Res. 2018;24[1]:43-51).
“These individuals typically have more difficulty with [drug] abstinence, more health consequences, and reduced quality of life, and social and professional consequences,” she said. “Some studies have suggested that they may not respond to lower doses of medication for attention-deficit/hyperactivity disorder and may require doses in the higher range.”
Research has hinted that several drugs that might prove helpful in these patients by improving both conditions, Dr. Mooney said. These include up to 180 mg/day of methylphenidate (Ritalin), 60- and 80-mg doses of mixed amphetamine salts/extended release, atomoxetine (Strattera), and bupropion.
In regard to bupropion, she said, “I find it to be a good choice in my substance use disorder patients for their depression and concentration problems. I have a greater number of individuals at 450 milligrams per day and the XL formulation.”
“We need more research to show if this is helpful,” she said. “It’s a reasonable choice in terms of weighing pros and cons, because it’s not [a controlled substance].”
Still, some of those medications are stimulants, Dr. Mooney said, and their use in patients with SUD is controversial. There are concerns about misuse and diversion.
“We want to have some flexibility,” she said, but it’s important to think about risks and priorities. In certain cases, ADHD may be a secondary concern.
“Some patients have a severe substance use disorder that keeps landing them in the emergency room or causing them to be hospitalized,” she said. “I’m more worried about that than the impairment function from ADHD.”
If you do consider stimulants, she said, longer-acting formulations can be less risky because there’s less potential for diversion. “Also, think about their treatment plan: Is their functioning improving? Are they or showing up for appointments? These are factors that will say: ‘Oh, I’m on the right path with this medication.’ ”
Behavioral treatment also can be helpful in these patients, she said, although “some may not be willing or motivated to put in the time that it takes to do the behavioral work.”
Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.
SAN DIEGO – Research suggests that as many as 23% of patients with substance use disorder (SUD) also have ADHD, adding an extra layer of complexity to a difficult-to-treat condition. What to do?
“Treating the ADHD can be useful in reducing the severity of symptoms without worsening the substance use disorder. It shouldn’t be avoided,” said psychiatrist Larissa J. Mooney, MD, of the University of California, Los Angeles, and the Veterans Affairs Greater Los Angeles Healthcare System, in a presentation at the annual Psych Congress.
When ADHD is on board, “it’s a more complicated and challenging clinical course,” Dr. Mooney said. The duo of disorders is linked to higher rates of polysubstance abuse and other psychiatric conditions, such as anxiety, bipolar disorder, posttraumatic stress, and antisocial/borderline conditions (Eur Addict Res. 2018;24[1]:43-51).
“These individuals typically have more difficulty with [drug] abstinence, more health consequences, and reduced quality of life, and social and professional consequences,” she said. “Some studies have suggested that they may not respond to lower doses of medication for attention-deficit/hyperactivity disorder and may require doses in the higher range.”
Research has hinted that several drugs that might prove helpful in these patients by improving both conditions, Dr. Mooney said. These include up to 180 mg/day of methylphenidate (Ritalin), 60- and 80-mg doses of mixed amphetamine salts/extended release, atomoxetine (Strattera), and bupropion.
In regard to bupropion, she said, “I find it to be a good choice in my substance use disorder patients for their depression and concentration problems. I have a greater number of individuals at 450 milligrams per day and the XL formulation.”
“We need more research to show if this is helpful,” she said. “It’s a reasonable choice in terms of weighing pros and cons, because it’s not [a controlled substance].”
Still, some of those medications are stimulants, Dr. Mooney said, and their use in patients with SUD is controversial. There are concerns about misuse and diversion.
“We want to have some flexibility,” she said, but it’s important to think about risks and priorities. In certain cases, ADHD may be a secondary concern.
“Some patients have a severe substance use disorder that keeps landing them in the emergency room or causing them to be hospitalized,” she said. “I’m more worried about that than the impairment function from ADHD.”
If you do consider stimulants, she said, longer-acting formulations can be less risky because there’s less potential for diversion. “Also, think about their treatment plan: Is their functioning improving? Are they or showing up for appointments? These are factors that will say: ‘Oh, I’m on the right path with this medication.’ ”
Behavioral treatment also can be helpful in these patients, she said, although “some may not be willing or motivated to put in the time that it takes to do the behavioral work.”
Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.
EXPERT ANALYSIS FROM PSYCH CONGRESS 2019
‘Joker’ filled with mental illness misconceptions
The Batman characters have been cultural icons for generations – spanning more than three-quarters of a century. How many of us had Batman (or the Joker) on our school lunch box or watched reruns of Adam West’s campy televised rendition of Batman? The October release of “Joker” has been breaking contemporary box office records.
(Spoiler alert!) The Todd Phillips film associates mental illness with violent acts, spurring a slew of articles explaining that this association is uncommon and may promote stigmatization and public fear of people with obvious symptoms of mental illness. The protagonist, Arthur Fleck (Joaquin Phoenix), suffers from a condition in which his affect and facial expressions are not appropriate to his emotions or to the situation. He laughs uncontrollably when a situation is sad or upsetting. Sometimes he laughs and cries at the same time. As a result, he often is misunderstood, ridiculed, and victimized – like many people with obvious mental illness.
Arthur Fleck is a loner who has difficulty with relationships and self-esteem, and is beaten severely while at work as a clown. Shortly after the incident, he is given a gun by one of his coworkers. He keeps it with him even when working as a clown in a children’s hospital – where it is accidentally revealed, and he is subsequently fired. Still in his clown garb, he later uses the gun when he is mocked and assaulted on the subway by three Gotham City bankers.
In an unusual tone, his mental health worker reminds him early in the film that he is prescribed seven different psychotropic medications, helping to cement for the viewer that mental illness is the cause of Arthur’s problems and the Joker’s origin story. Then the funding for Arthur’s mental health treatment (even if it was not good treatment) was cut – a problem not just in Gotham.
While some of Arthur Fleck’s symptoms are consistent with real mental illness, the combination of symptoms is unusual. Although he is being treated with a variety of medications, it is unclear whether any of them are helping him or what exactly they are helping him with. (Ironically, once he is off of his medications, he becomes a better dresser and a better dancer.) He writes in a disorganized way in his journal; the only intelligible sentence that is focused on is, “The worst part about having mental illness is people expect you to behave as if you DONT.” A smiley face in the ‘O’ suggests that his affect is inappropriate even in his writing. Arthur’s condition of uncontrollable laughing and/or crying, associated with head trauma, appears more consistent with the neurologic condition pseudobulbar affect rather than a mental illness. In addition to pseudobulbar affect, Arthur demonstrates a constellation of symptoms of different kinds of mental illness, including erotomanic delusions, ideas of reference, and disorganized thinking. He also does not appear to take social cues, such as knowing when he is being mocked. He appears to believe that his neighbor is his girlfriend (as the viewer was similarly led to believe), eventually breaking into her apartment where he thought he belonged, much to her horror when she finds him there. Some of his symptoms may run in his family (whether it be his biological or adoptive family).
Penny (Arthur’s mother) strongly believes (perhaps a delusion, perhaps not) that her previous employer Thomas Wayne (the future Batman’s father) is the father of her love-child, Arthur. When Arthur obtains Penny’s mental health records (through his own violent devices), he finds that she had been diagnosed with narcissistic personality disorder and a psychotic disorder. She had been found guilty of endangering the welfare of her (perhaps adopted, perhaps not) child Arthur, who had been malnourished, with severe head trauma, and tied to a radiator.
Arthur’s smothering of his mother with a pillow in her hospital bed, after he was devastated by both her stroke and this newfound data, occurred in a perfect storm. The killing is not portrayed as an act of euthanasia. We know that schizophrenia is overrepresented among matricide perpetrators and that long-term dysfunctional relationships between mother and (grown) child usually precede matricides. Mothers are often seen as controlling, fathers are often absent (as in Arthur’s case), and the child is often overly dependent. The mother and child (as seen here) often have a relationship marked by love and hate – mutual dependence and hostility. But Arthur is not the only character in the Batman universe to commit matricide. Recall that the Batman’s psychiatrist Amadeus Arkham himself killed his own mentally ill mother during his young adulthood.
Pop culture can give the public negative impressions of mental illness. While filmmakers need not portray actual mental illnesses or their symptoms in moving their stories forward, their portrayals have an impact on what the public sees as mental illness. This is similar to the current American president and others in political power asserting that mental illness causes mass shootings, and those in the public taking their word for it rather than the word of psychiatry.
In actuality, what felt the most true to life in the film was the early scene in which Arthur was seriously assaulted while waving the going-out-of-business sign on the sidewalk, just trying to make a living. As psychiatrists know, people with mental illness are more likely to be victimized by others in society than to be perpetrators of violence. To be sure, some of Arthur’s characteristics are dynamic risk factors, such as his unemployment and social isolation. However, society often conflates mental illness with dangerousness, but most people with mental illness are not violent.
In the final scenes, Arthur Fleck (who is now the Joker) is apparently back in the white-walled Arkham State Hospital, with an implication that he has gotten away with the murders, either found incompetent or insane. This, too, has negative implications for the public viewing the film – and further perpetuates the misunderstanding that people with mental illness “get away” with their crimes. In reality, depending on the study, approximately one-quarter of those who pleaded insanity were found insane, and those facing jury trials (and public perception) are less likely to be found insane than those with bench trials. Public misinterpretations and outrage over the idea that a mentally unwell person might be found insane rather than guilty have existed for centuries, perhaps most memorably when John Hinckley Jr. attempted to assassinate former President Ronald Reagan, after identifying with a character in the film “Taxi Driver.” Let’s presume that Gotham has an insanity defense similar to other places in America. Then, in order to be found insane, Arthur’s pseudobulbar affect or his (unclear) mental illness would have either caused him not to know the nature and consequences of his acts, and/or to appreciate the wrongfulness of his acts (if we are fairly certain that Gotham is actually New York City). Neither of these appear to be true from the film. He knew that he was killing. No delusions or hallucinations made him think his acts were not wrong. Rather, he had an arguably rational motive – certainly the multitudes wearing clown masks in the subsequent uprisings against the powerful also believed his motive to be rational. He deliberately killed the bankers who mocked and beat him. He was also able to defer his killings until what he calculated was the right time to have the most impact – for example, on live television, or when he was alone with his mother in the hospital.
In closing, unrealistic portrayals of the link between mental illness, violence, and forensic hospitalization are seen on the silver screen in “Joker.” We hope that others who feign mental illness symptoms to evade criminal responsibility will emulate Joaquin Phoenix’s Joker as it will make it much easier for forensic psychiatrists to ferret out malingerers!
Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington, D.C.: American Psychiatric Association Publishing [2019]), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law. Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill-Cornell Medical Center.
The Batman characters have been cultural icons for generations – spanning more than three-quarters of a century. How many of us had Batman (or the Joker) on our school lunch box or watched reruns of Adam West’s campy televised rendition of Batman? The October release of “Joker” has been breaking contemporary box office records.
(Spoiler alert!) The Todd Phillips film associates mental illness with violent acts, spurring a slew of articles explaining that this association is uncommon and may promote stigmatization and public fear of people with obvious symptoms of mental illness. The protagonist, Arthur Fleck (Joaquin Phoenix), suffers from a condition in which his affect and facial expressions are not appropriate to his emotions or to the situation. He laughs uncontrollably when a situation is sad or upsetting. Sometimes he laughs and cries at the same time. As a result, he often is misunderstood, ridiculed, and victimized – like many people with obvious mental illness.
Arthur Fleck is a loner who has difficulty with relationships and self-esteem, and is beaten severely while at work as a clown. Shortly after the incident, he is given a gun by one of his coworkers. He keeps it with him even when working as a clown in a children’s hospital – where it is accidentally revealed, and he is subsequently fired. Still in his clown garb, he later uses the gun when he is mocked and assaulted on the subway by three Gotham City bankers.
In an unusual tone, his mental health worker reminds him early in the film that he is prescribed seven different psychotropic medications, helping to cement for the viewer that mental illness is the cause of Arthur’s problems and the Joker’s origin story. Then the funding for Arthur’s mental health treatment (even if it was not good treatment) was cut – a problem not just in Gotham.
While some of Arthur Fleck’s symptoms are consistent with real mental illness, the combination of symptoms is unusual. Although he is being treated with a variety of medications, it is unclear whether any of them are helping him or what exactly they are helping him with. (Ironically, once he is off of his medications, he becomes a better dresser and a better dancer.) He writes in a disorganized way in his journal; the only intelligible sentence that is focused on is, “The worst part about having mental illness is people expect you to behave as if you DONT.” A smiley face in the ‘O’ suggests that his affect is inappropriate even in his writing. Arthur’s condition of uncontrollable laughing and/or crying, associated with head trauma, appears more consistent with the neurologic condition pseudobulbar affect rather than a mental illness. In addition to pseudobulbar affect, Arthur demonstrates a constellation of symptoms of different kinds of mental illness, including erotomanic delusions, ideas of reference, and disorganized thinking. He also does not appear to take social cues, such as knowing when he is being mocked. He appears to believe that his neighbor is his girlfriend (as the viewer was similarly led to believe), eventually breaking into her apartment where he thought he belonged, much to her horror when she finds him there. Some of his symptoms may run in his family (whether it be his biological or adoptive family).
Penny (Arthur’s mother) strongly believes (perhaps a delusion, perhaps not) that her previous employer Thomas Wayne (the future Batman’s father) is the father of her love-child, Arthur. When Arthur obtains Penny’s mental health records (through his own violent devices), he finds that she had been diagnosed with narcissistic personality disorder and a psychotic disorder. She had been found guilty of endangering the welfare of her (perhaps adopted, perhaps not) child Arthur, who had been malnourished, with severe head trauma, and tied to a radiator.
Arthur’s smothering of his mother with a pillow in her hospital bed, after he was devastated by both her stroke and this newfound data, occurred in a perfect storm. The killing is not portrayed as an act of euthanasia. We know that schizophrenia is overrepresented among matricide perpetrators and that long-term dysfunctional relationships between mother and (grown) child usually precede matricides. Mothers are often seen as controlling, fathers are often absent (as in Arthur’s case), and the child is often overly dependent. The mother and child (as seen here) often have a relationship marked by love and hate – mutual dependence and hostility. But Arthur is not the only character in the Batman universe to commit matricide. Recall that the Batman’s psychiatrist Amadeus Arkham himself killed his own mentally ill mother during his young adulthood.
Pop culture can give the public negative impressions of mental illness. While filmmakers need not portray actual mental illnesses or their symptoms in moving their stories forward, their portrayals have an impact on what the public sees as mental illness. This is similar to the current American president and others in political power asserting that mental illness causes mass shootings, and those in the public taking their word for it rather than the word of psychiatry.
In actuality, what felt the most true to life in the film was the early scene in which Arthur was seriously assaulted while waving the going-out-of-business sign on the sidewalk, just trying to make a living. As psychiatrists know, people with mental illness are more likely to be victimized by others in society than to be perpetrators of violence. To be sure, some of Arthur’s characteristics are dynamic risk factors, such as his unemployment and social isolation. However, society often conflates mental illness with dangerousness, but most people with mental illness are not violent.
In the final scenes, Arthur Fleck (who is now the Joker) is apparently back in the white-walled Arkham State Hospital, with an implication that he has gotten away with the murders, either found incompetent or insane. This, too, has negative implications for the public viewing the film – and further perpetuates the misunderstanding that people with mental illness “get away” with their crimes. In reality, depending on the study, approximately one-quarter of those who pleaded insanity were found insane, and those facing jury trials (and public perception) are less likely to be found insane than those with bench trials. Public misinterpretations and outrage over the idea that a mentally unwell person might be found insane rather than guilty have existed for centuries, perhaps most memorably when John Hinckley Jr. attempted to assassinate former President Ronald Reagan, after identifying with a character in the film “Taxi Driver.” Let’s presume that Gotham has an insanity defense similar to other places in America. Then, in order to be found insane, Arthur’s pseudobulbar affect or his (unclear) mental illness would have either caused him not to know the nature and consequences of his acts, and/or to appreciate the wrongfulness of his acts (if we are fairly certain that Gotham is actually New York City). Neither of these appear to be true from the film. He knew that he was killing. No delusions or hallucinations made him think his acts were not wrong. Rather, he had an arguably rational motive – certainly the multitudes wearing clown masks in the subsequent uprisings against the powerful also believed his motive to be rational. He deliberately killed the bankers who mocked and beat him. He was also able to defer his killings until what he calculated was the right time to have the most impact – for example, on live television, or when he was alone with his mother in the hospital.
In closing, unrealistic portrayals of the link between mental illness, violence, and forensic hospitalization are seen on the silver screen in “Joker.” We hope that others who feign mental illness symptoms to evade criminal responsibility will emulate Joaquin Phoenix’s Joker as it will make it much easier for forensic psychiatrists to ferret out malingerers!
Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington, D.C.: American Psychiatric Association Publishing [2019]), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law. Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill-Cornell Medical Center.
The Batman characters have been cultural icons for generations – spanning more than three-quarters of a century. How many of us had Batman (or the Joker) on our school lunch box or watched reruns of Adam West’s campy televised rendition of Batman? The October release of “Joker” has been breaking contemporary box office records.
(Spoiler alert!) The Todd Phillips film associates mental illness with violent acts, spurring a slew of articles explaining that this association is uncommon and may promote stigmatization and public fear of people with obvious symptoms of mental illness. The protagonist, Arthur Fleck (Joaquin Phoenix), suffers from a condition in which his affect and facial expressions are not appropriate to his emotions or to the situation. He laughs uncontrollably when a situation is sad or upsetting. Sometimes he laughs and cries at the same time. As a result, he often is misunderstood, ridiculed, and victimized – like many people with obvious mental illness.
Arthur Fleck is a loner who has difficulty with relationships and self-esteem, and is beaten severely while at work as a clown. Shortly after the incident, he is given a gun by one of his coworkers. He keeps it with him even when working as a clown in a children’s hospital – where it is accidentally revealed, and he is subsequently fired. Still in his clown garb, he later uses the gun when he is mocked and assaulted on the subway by three Gotham City bankers.
In an unusual tone, his mental health worker reminds him early in the film that he is prescribed seven different psychotropic medications, helping to cement for the viewer that mental illness is the cause of Arthur’s problems and the Joker’s origin story. Then the funding for Arthur’s mental health treatment (even if it was not good treatment) was cut – a problem not just in Gotham.
While some of Arthur Fleck’s symptoms are consistent with real mental illness, the combination of symptoms is unusual. Although he is being treated with a variety of medications, it is unclear whether any of them are helping him or what exactly they are helping him with. (Ironically, once he is off of his medications, he becomes a better dresser and a better dancer.) He writes in a disorganized way in his journal; the only intelligible sentence that is focused on is, “The worst part about having mental illness is people expect you to behave as if you DONT.” A smiley face in the ‘O’ suggests that his affect is inappropriate even in his writing. Arthur’s condition of uncontrollable laughing and/or crying, associated with head trauma, appears more consistent with the neurologic condition pseudobulbar affect rather than a mental illness. In addition to pseudobulbar affect, Arthur demonstrates a constellation of symptoms of different kinds of mental illness, including erotomanic delusions, ideas of reference, and disorganized thinking. He also does not appear to take social cues, such as knowing when he is being mocked. He appears to believe that his neighbor is his girlfriend (as the viewer was similarly led to believe), eventually breaking into her apartment where he thought he belonged, much to her horror when she finds him there. Some of his symptoms may run in his family (whether it be his biological or adoptive family).
Penny (Arthur’s mother) strongly believes (perhaps a delusion, perhaps not) that her previous employer Thomas Wayne (the future Batman’s father) is the father of her love-child, Arthur. When Arthur obtains Penny’s mental health records (through his own violent devices), he finds that she had been diagnosed with narcissistic personality disorder and a psychotic disorder. She had been found guilty of endangering the welfare of her (perhaps adopted, perhaps not) child Arthur, who had been malnourished, with severe head trauma, and tied to a radiator.
Arthur’s smothering of his mother with a pillow in her hospital bed, after he was devastated by both her stroke and this newfound data, occurred in a perfect storm. The killing is not portrayed as an act of euthanasia. We know that schizophrenia is overrepresented among matricide perpetrators and that long-term dysfunctional relationships between mother and (grown) child usually precede matricides. Mothers are often seen as controlling, fathers are often absent (as in Arthur’s case), and the child is often overly dependent. The mother and child (as seen here) often have a relationship marked by love and hate – mutual dependence and hostility. But Arthur is not the only character in the Batman universe to commit matricide. Recall that the Batman’s psychiatrist Amadeus Arkham himself killed his own mentally ill mother during his young adulthood.
Pop culture can give the public negative impressions of mental illness. While filmmakers need not portray actual mental illnesses or their symptoms in moving their stories forward, their portrayals have an impact on what the public sees as mental illness. This is similar to the current American president and others in political power asserting that mental illness causes mass shootings, and those in the public taking their word for it rather than the word of psychiatry.
In actuality, what felt the most true to life in the film was the early scene in which Arthur was seriously assaulted while waving the going-out-of-business sign on the sidewalk, just trying to make a living. As psychiatrists know, people with mental illness are more likely to be victimized by others in society than to be perpetrators of violence. To be sure, some of Arthur’s characteristics are dynamic risk factors, such as his unemployment and social isolation. However, society often conflates mental illness with dangerousness, but most people with mental illness are not violent.
In the final scenes, Arthur Fleck (who is now the Joker) is apparently back in the white-walled Arkham State Hospital, with an implication that he has gotten away with the murders, either found incompetent or insane. This, too, has negative implications for the public viewing the film – and further perpetuates the misunderstanding that people with mental illness “get away” with their crimes. In reality, depending on the study, approximately one-quarter of those who pleaded insanity were found insane, and those facing jury trials (and public perception) are less likely to be found insane than those with bench trials. Public misinterpretations and outrage over the idea that a mentally unwell person might be found insane rather than guilty have existed for centuries, perhaps most memorably when John Hinckley Jr. attempted to assassinate former President Ronald Reagan, after identifying with a character in the film “Taxi Driver.” Let’s presume that Gotham has an insanity defense similar to other places in America. Then, in order to be found insane, Arthur’s pseudobulbar affect or his (unclear) mental illness would have either caused him not to know the nature and consequences of his acts, and/or to appreciate the wrongfulness of his acts (if we are fairly certain that Gotham is actually New York City). Neither of these appear to be true from the film. He knew that he was killing. No delusions or hallucinations made him think his acts were not wrong. Rather, he had an arguably rational motive – certainly the multitudes wearing clown masks in the subsequent uprisings against the powerful also believed his motive to be rational. He deliberately killed the bankers who mocked and beat him. He was also able to defer his killings until what he calculated was the right time to have the most impact – for example, on live television, or when he was alone with his mother in the hospital.
In closing, unrealistic portrayals of the link between mental illness, violence, and forensic hospitalization are seen on the silver screen in “Joker.” We hope that others who feign mental illness symptoms to evade criminal responsibility will emulate Joaquin Phoenix’s Joker as it will make it much easier for forensic psychiatrists to ferret out malingerers!
Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington, D.C.: American Psychiatric Association Publishing [2019]), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law. Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill-Cornell Medical Center.
Investigative device cut risk of contrast-induced AKI
SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.
The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m2 or less and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.
The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).
“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”
A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”
For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”
The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.
SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.
SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.
The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m2 or less and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.
The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).
“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”
A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”
For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”
The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.
SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.
SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.
The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m2 or less and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.
The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).
“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”
A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”
For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”
The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.
SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.
REPORTING FROM TCT 2019
Food addiction is pervasive among psychiatric patients
COPENHAGEN – Food addiction is threefold more prevalent among individuals with clinically diagnosed mental disorders than in the general population, according to a report from the Food Addiction Denmark (FADK) project.
This finding provides support for the hypothesis that food addiction is a key link in the chain connecting psychiatric disorders to increased risk of obesity, which in turn contributes to the substantially shorter life expectancy of psychiatric patients, Christina Horsager, MD, a cofounder of the project, said at the annual congress of the European College of Neuropsychopharmacology.
The FADK project is designed to fill in major gaps in the understanding of food addiction. The project included a 2018 Danish nationwide questionnaire survey of 1,394 individuals with various mental disorders and 1,699 others from the general population. The questionnaire included the Yale Food Addiction Scale Version 2.0 (Psychol Addict Behav. 2016 Feb;30[1]:113-21), which was used to identify affected individuals, as well as psychopathology rating scales, explained Dr. Horsager, of the child and adolescent psychiatry department at Aalborg (Denmark) University Hospital.
The prevalence of food addiction was 9% in the general population and 26.5% in individuals with mental disorders. The highest prevalence was, not surprisingly, in individuals with a DSM-5 diagnosis of an eating disorder. The rate was 30% in individuals with a DSM-5 personality disorder, 28% in those with a mood disorder, 17% with autism and other pervasive developmental disorders, just under 12% with a psychoactive substance use disorder, and 16% among patients with ADHD and other behavioral disorders.
But then again, the medications for ADHD tend to suppress appetite.
Obesity was significantly more prevalent among survey respondents who met criteria for food addiction, by a margin of 44.7% to 33.4%.
Food addiction is not an official DSM disorder. In fact, it’s a highly controversial construct: Some behavioral scientists think it has the classic hallmarks of a bona fide eating or substance use disorder; others don’t. Dr. Horsager highlighted the first systematic review of the evidence regarding food addiction, in which the University of Florida, Gainesville, authors concluded: “Overall, findings support food addiction as a unique construct consistent with criteria for other substance use disorder diagnoses. ... Though both behavioral and substance-related factors are implicated in the addictive process, symptoms appear to better fit criteria for substance use disorder than behavioral addiction” (Nutrients. 2018 Apr 12;10[4]:477. doi: 10.3390/nu10040477).
Food addiction is characterized by a compulsion to overeat calorie-dense, highly processed, super-palatable, sugar- and fat-laden foods. In this era of an ongoing global obesity epidemic, the public has become enthralled with the concept; a recent Google search of the term “food addiction” coughed up 288 million results.
The Food Addiction Denmark project findings warrant prospective studies examining whether treatment of food addiction might improve the prognosis of patients with mental disorders, according to Dr. Horsager.
She reported having no financial conflicts regarding her presentation.
COPENHAGEN – Food addiction is threefold more prevalent among individuals with clinically diagnosed mental disorders than in the general population, according to a report from the Food Addiction Denmark (FADK) project.
This finding provides support for the hypothesis that food addiction is a key link in the chain connecting psychiatric disorders to increased risk of obesity, which in turn contributes to the substantially shorter life expectancy of psychiatric patients, Christina Horsager, MD, a cofounder of the project, said at the annual congress of the European College of Neuropsychopharmacology.
The FADK project is designed to fill in major gaps in the understanding of food addiction. The project included a 2018 Danish nationwide questionnaire survey of 1,394 individuals with various mental disorders and 1,699 others from the general population. The questionnaire included the Yale Food Addiction Scale Version 2.0 (Psychol Addict Behav. 2016 Feb;30[1]:113-21), which was used to identify affected individuals, as well as psychopathology rating scales, explained Dr. Horsager, of the child and adolescent psychiatry department at Aalborg (Denmark) University Hospital.
The prevalence of food addiction was 9% in the general population and 26.5% in individuals with mental disorders. The highest prevalence was, not surprisingly, in individuals with a DSM-5 diagnosis of an eating disorder. The rate was 30% in individuals with a DSM-5 personality disorder, 28% in those with a mood disorder, 17% with autism and other pervasive developmental disorders, just under 12% with a psychoactive substance use disorder, and 16% among patients with ADHD and other behavioral disorders.
But then again, the medications for ADHD tend to suppress appetite.
Obesity was significantly more prevalent among survey respondents who met criteria for food addiction, by a margin of 44.7% to 33.4%.
Food addiction is not an official DSM disorder. In fact, it’s a highly controversial construct: Some behavioral scientists think it has the classic hallmarks of a bona fide eating or substance use disorder; others don’t. Dr. Horsager highlighted the first systematic review of the evidence regarding food addiction, in which the University of Florida, Gainesville, authors concluded: “Overall, findings support food addiction as a unique construct consistent with criteria for other substance use disorder diagnoses. ... Though both behavioral and substance-related factors are implicated in the addictive process, symptoms appear to better fit criteria for substance use disorder than behavioral addiction” (Nutrients. 2018 Apr 12;10[4]:477. doi: 10.3390/nu10040477).
Food addiction is characterized by a compulsion to overeat calorie-dense, highly processed, super-palatable, sugar- and fat-laden foods. In this era of an ongoing global obesity epidemic, the public has become enthralled with the concept; a recent Google search of the term “food addiction” coughed up 288 million results.
The Food Addiction Denmark project findings warrant prospective studies examining whether treatment of food addiction might improve the prognosis of patients with mental disorders, according to Dr. Horsager.
She reported having no financial conflicts regarding her presentation.
COPENHAGEN – Food addiction is threefold more prevalent among individuals with clinically diagnosed mental disorders than in the general population, according to a report from the Food Addiction Denmark (FADK) project.
This finding provides support for the hypothesis that food addiction is a key link in the chain connecting psychiatric disorders to increased risk of obesity, which in turn contributes to the substantially shorter life expectancy of psychiatric patients, Christina Horsager, MD, a cofounder of the project, said at the annual congress of the European College of Neuropsychopharmacology.
The FADK project is designed to fill in major gaps in the understanding of food addiction. The project included a 2018 Danish nationwide questionnaire survey of 1,394 individuals with various mental disorders and 1,699 others from the general population. The questionnaire included the Yale Food Addiction Scale Version 2.0 (Psychol Addict Behav. 2016 Feb;30[1]:113-21), which was used to identify affected individuals, as well as psychopathology rating scales, explained Dr. Horsager, of the child and adolescent psychiatry department at Aalborg (Denmark) University Hospital.
The prevalence of food addiction was 9% in the general population and 26.5% in individuals with mental disorders. The highest prevalence was, not surprisingly, in individuals with a DSM-5 diagnosis of an eating disorder. The rate was 30% in individuals with a DSM-5 personality disorder, 28% in those with a mood disorder, 17% with autism and other pervasive developmental disorders, just under 12% with a psychoactive substance use disorder, and 16% among patients with ADHD and other behavioral disorders.
But then again, the medications for ADHD tend to suppress appetite.
Obesity was significantly more prevalent among survey respondents who met criteria for food addiction, by a margin of 44.7% to 33.4%.
Food addiction is not an official DSM disorder. In fact, it’s a highly controversial construct: Some behavioral scientists think it has the classic hallmarks of a bona fide eating or substance use disorder; others don’t. Dr. Horsager highlighted the first systematic review of the evidence regarding food addiction, in which the University of Florida, Gainesville, authors concluded: “Overall, findings support food addiction as a unique construct consistent with criteria for other substance use disorder diagnoses. ... Though both behavioral and substance-related factors are implicated in the addictive process, symptoms appear to better fit criteria for substance use disorder than behavioral addiction” (Nutrients. 2018 Apr 12;10[4]:477. doi: 10.3390/nu10040477).
Food addiction is characterized by a compulsion to overeat calorie-dense, highly processed, super-palatable, sugar- and fat-laden foods. In this era of an ongoing global obesity epidemic, the public has become enthralled with the concept; a recent Google search of the term “food addiction” coughed up 288 million results.
The Food Addiction Denmark project findings warrant prospective studies examining whether treatment of food addiction might improve the prognosis of patients with mental disorders, according to Dr. Horsager.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM ECNP 2019
Plug-unplug catheters: A good option, study suggests
Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.
“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.
A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.
The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.
All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.
The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.
The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.
Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.
There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.
The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”
Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.
Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”
Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.
The authors did not report any potential conflicts of interest.
SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.
* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.
Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.
“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.
A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.
The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.
All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.
The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.
The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.
Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.
There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.
The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”
Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.
Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”
Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.
The authors did not report any potential conflicts of interest.
SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.
* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.
Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.
“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.
A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.
The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.
All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.
The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.
The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.
Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.
There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.
The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”
Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.
Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”
Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.
The authors did not report any potential conflicts of interest.
SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.
* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.
FROM OBSTETRICS & GYNECOLOGY
Next-gen genomic test plus bronchoscopy may improve lung nodule management
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
REPORTING FROM CHEST 2019
The growing NP and PA workforce in hospital medicine
High rate of turnover among NPs, PAs
If you were a physician hospitalist in a group serving adults in 2017 you probably worked with nurse practitioners (NPs) and/or physician assistants (PAs). Seventy-seven percent of hospital medicine groups (HMGs) employed NPs and PAs that year.
In addition, the larger the group, the more likely the group was to have NPs and PAs as part of their practice model – 89% of hospital medicine groups with more than 30 physician had NPs and/or PAs as partners. In addition, the mean number of physicians for adult hospital medicine groups was 17.9. The same practices employed an average of 3.5 NPs, and 2.6 PAs.
Based on these numbers, there are just under three physicians per NP and PA in the typical HMG serving adults. This is all according to data from the 2018 State of Hospital Medicine (SoHM) report that was published in 2019 by the Society of Hospital Medicine.
These observations lead to a number of questions. One thing that is not clear from the SoHM is why NPs and PAs are becoming a larger part of the hospital medicine workforce, but there are some insights and conjecture that can be drawn from the data. The first is economics. Over 6 years, the median incomes of NPs and PAs have risen a relatively modest 10%; over the same period physician hospitalists have seen a whopping 23.6% median pay increase.
One argument against economics as a driving force behind greater use of NPs and PAs in the hospital medicine workforce is the billing patterns of HMGs that use NPs and PAs. Ten percent of HMGs do not have their NPs and PAs bill at all. The distribution of HMGs that predominantly bill NP and PA services as shared visits, versus having NPs and PAs bill independently, has also not changed much over the years, with 22% of HMGs having NPs and PAs bill independently as a predominant model. This would seem to suggest that some HMGs may not have learned how to deploy NPs and PAs effectively.
While inefficiency can be due to hospital bylaws, the culture of the hospital medicine group, or the skill set of the NPs and PAs working in HMGs – it would seem that if the driving force for the increase in the utilization of NPs and PAs in HMGs was financial, then that would also result in more of these providers billing independently, or alternatively, an increase in hospitalist physician productivity, which the data do not show. However, multistate HMGs may have this figured out better than some of the rest of us – 78% of these HMGs have NPs and PAs billing independently! All other categories of HMGs together are around 13%, with the next highest being hospital or health system integrated delivery systems, where NPs/PAs bill independently about 15% of the time.
In the last 2 years of the survey, there have been marked increases in the number of NPs and PAs at HMGs performing “nontraditional” services. For example, outpatient work has increased from 11% to 17%, and work in the postacute space has increased from 13% to 25%. Work in behavioral health and alcohol and drug rehab facilities has also increased, from 17% to 26%. As HMGs seek to rationalize their workforce while expanding, it is possible that decision makers have felt that it was either more economical to place NPs and PAs in positions where they are seeing these patients, or it was more aligned with the NP/PA skill set, or both. In any event, as the scope of hospital medicine broadens, the use of PAs and NPs has also increased – which is probably not coincidental.
The average hospital medicine group continues to have staff openings. Workforce shortages may be leading to what in the past may have been considered physician openings being filled by NPs and PAs. Only 33% of HMGs reported having all their physician openings filled. Median physician shortage was 12% of total approved staffing. Given concerns in hospital medicine about provider burnout, the number of hospital medicine openings is no doubt a concern to HMG leaders and hospitalists. And necessity being the mother of invention, HMG leadership must be thinking differently than in the past about open positions and the skill mix needed to fill them. I believe this is leading to NPs and PAs being considered more often for a role that would have been open only to a physician in the past.
Just as open positions are a concern, so is turnover. One striking finding in the SoHM is the very high rate of turnover among NPs and PAs – a whopping 19.1% per year. For physicians, the same rate was 7.4% and has been declining every survey for many years. While NPs and PAs may be intended to stabilize the workforce, because of how this is being done in some groups, NPs and PAs may instead be a destabilizing factor. Rapid growth can lead to haphazard onboarding and less than clearly defined roles. NPs and PAs may often be placed into roles for which they are not yet prepared. In addition, the pay disparity between NPs and PAs and physicians has increased. As a new field, and with many HMGs still rapidly growing, increased thoughtfulness and maturity about how NPs and PAs are integrated into hospital medicine practices should lead to less turnover and better HMG stability in the future.
These observations could mark a future that includes higher pay for hospital medicine PAs and NPs (and potentially a slowdown in salary growth for physicians); HMGs taking steps to make the financial model more attractive by having NPs and PAs bill independently more often; and HMGs and their leaders engaging NPs and PAs by more clearly defining roles, shoring up onboarding and mentoring programs, and other measures that decrease turnover. This would help to make hospital medicine a career destination, rather than a stopping off point for NPs and PAs, much as it has become for internists over the past 20 years.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.
High rate of turnover among NPs, PAs
High rate of turnover among NPs, PAs
If you were a physician hospitalist in a group serving adults in 2017 you probably worked with nurse practitioners (NPs) and/or physician assistants (PAs). Seventy-seven percent of hospital medicine groups (HMGs) employed NPs and PAs that year.
In addition, the larger the group, the more likely the group was to have NPs and PAs as part of their practice model – 89% of hospital medicine groups with more than 30 physician had NPs and/or PAs as partners. In addition, the mean number of physicians for adult hospital medicine groups was 17.9. The same practices employed an average of 3.5 NPs, and 2.6 PAs.
Based on these numbers, there are just under three physicians per NP and PA in the typical HMG serving adults. This is all according to data from the 2018 State of Hospital Medicine (SoHM) report that was published in 2019 by the Society of Hospital Medicine.
These observations lead to a number of questions. One thing that is not clear from the SoHM is why NPs and PAs are becoming a larger part of the hospital medicine workforce, but there are some insights and conjecture that can be drawn from the data. The first is economics. Over 6 years, the median incomes of NPs and PAs have risen a relatively modest 10%; over the same period physician hospitalists have seen a whopping 23.6% median pay increase.
One argument against economics as a driving force behind greater use of NPs and PAs in the hospital medicine workforce is the billing patterns of HMGs that use NPs and PAs. Ten percent of HMGs do not have their NPs and PAs bill at all. The distribution of HMGs that predominantly bill NP and PA services as shared visits, versus having NPs and PAs bill independently, has also not changed much over the years, with 22% of HMGs having NPs and PAs bill independently as a predominant model. This would seem to suggest that some HMGs may not have learned how to deploy NPs and PAs effectively.
While inefficiency can be due to hospital bylaws, the culture of the hospital medicine group, or the skill set of the NPs and PAs working in HMGs – it would seem that if the driving force for the increase in the utilization of NPs and PAs in HMGs was financial, then that would also result in more of these providers billing independently, or alternatively, an increase in hospitalist physician productivity, which the data do not show. However, multistate HMGs may have this figured out better than some of the rest of us – 78% of these HMGs have NPs and PAs billing independently! All other categories of HMGs together are around 13%, with the next highest being hospital or health system integrated delivery systems, where NPs/PAs bill independently about 15% of the time.
In the last 2 years of the survey, there have been marked increases in the number of NPs and PAs at HMGs performing “nontraditional” services. For example, outpatient work has increased from 11% to 17%, and work in the postacute space has increased from 13% to 25%. Work in behavioral health and alcohol and drug rehab facilities has also increased, from 17% to 26%. As HMGs seek to rationalize their workforce while expanding, it is possible that decision makers have felt that it was either more economical to place NPs and PAs in positions where they are seeing these patients, or it was more aligned with the NP/PA skill set, or both. In any event, as the scope of hospital medicine broadens, the use of PAs and NPs has also increased – which is probably not coincidental.
The average hospital medicine group continues to have staff openings. Workforce shortages may be leading to what in the past may have been considered physician openings being filled by NPs and PAs. Only 33% of HMGs reported having all their physician openings filled. Median physician shortage was 12% of total approved staffing. Given concerns in hospital medicine about provider burnout, the number of hospital medicine openings is no doubt a concern to HMG leaders and hospitalists. And necessity being the mother of invention, HMG leadership must be thinking differently than in the past about open positions and the skill mix needed to fill them. I believe this is leading to NPs and PAs being considered more often for a role that would have been open only to a physician in the past.
Just as open positions are a concern, so is turnover. One striking finding in the SoHM is the very high rate of turnover among NPs and PAs – a whopping 19.1% per year. For physicians, the same rate was 7.4% and has been declining every survey for many years. While NPs and PAs may be intended to stabilize the workforce, because of how this is being done in some groups, NPs and PAs may instead be a destabilizing factor. Rapid growth can lead to haphazard onboarding and less than clearly defined roles. NPs and PAs may often be placed into roles for which they are not yet prepared. In addition, the pay disparity between NPs and PAs and physicians has increased. As a new field, and with many HMGs still rapidly growing, increased thoughtfulness and maturity about how NPs and PAs are integrated into hospital medicine practices should lead to less turnover and better HMG stability in the future.
These observations could mark a future that includes higher pay for hospital medicine PAs and NPs (and potentially a slowdown in salary growth for physicians); HMGs taking steps to make the financial model more attractive by having NPs and PAs bill independently more often; and HMGs and their leaders engaging NPs and PAs by more clearly defining roles, shoring up onboarding and mentoring programs, and other measures that decrease turnover. This would help to make hospital medicine a career destination, rather than a stopping off point for NPs and PAs, much as it has become for internists over the past 20 years.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.
If you were a physician hospitalist in a group serving adults in 2017 you probably worked with nurse practitioners (NPs) and/or physician assistants (PAs). Seventy-seven percent of hospital medicine groups (HMGs) employed NPs and PAs that year.
In addition, the larger the group, the more likely the group was to have NPs and PAs as part of their practice model – 89% of hospital medicine groups with more than 30 physician had NPs and/or PAs as partners. In addition, the mean number of physicians for adult hospital medicine groups was 17.9. The same practices employed an average of 3.5 NPs, and 2.6 PAs.
Based on these numbers, there are just under three physicians per NP and PA in the typical HMG serving adults. This is all according to data from the 2018 State of Hospital Medicine (SoHM) report that was published in 2019 by the Society of Hospital Medicine.
These observations lead to a number of questions. One thing that is not clear from the SoHM is why NPs and PAs are becoming a larger part of the hospital medicine workforce, but there are some insights and conjecture that can be drawn from the data. The first is economics. Over 6 years, the median incomes of NPs and PAs have risen a relatively modest 10%; over the same period physician hospitalists have seen a whopping 23.6% median pay increase.
One argument against economics as a driving force behind greater use of NPs and PAs in the hospital medicine workforce is the billing patterns of HMGs that use NPs and PAs. Ten percent of HMGs do not have their NPs and PAs bill at all. The distribution of HMGs that predominantly bill NP and PA services as shared visits, versus having NPs and PAs bill independently, has also not changed much over the years, with 22% of HMGs having NPs and PAs bill independently as a predominant model. This would seem to suggest that some HMGs may not have learned how to deploy NPs and PAs effectively.
While inefficiency can be due to hospital bylaws, the culture of the hospital medicine group, or the skill set of the NPs and PAs working in HMGs – it would seem that if the driving force for the increase in the utilization of NPs and PAs in HMGs was financial, then that would also result in more of these providers billing independently, or alternatively, an increase in hospitalist physician productivity, which the data do not show. However, multistate HMGs may have this figured out better than some of the rest of us – 78% of these HMGs have NPs and PAs billing independently! All other categories of HMGs together are around 13%, with the next highest being hospital or health system integrated delivery systems, where NPs/PAs bill independently about 15% of the time.
In the last 2 years of the survey, there have been marked increases in the number of NPs and PAs at HMGs performing “nontraditional” services. For example, outpatient work has increased from 11% to 17%, and work in the postacute space has increased from 13% to 25%. Work in behavioral health and alcohol and drug rehab facilities has also increased, from 17% to 26%. As HMGs seek to rationalize their workforce while expanding, it is possible that decision makers have felt that it was either more economical to place NPs and PAs in positions where they are seeing these patients, or it was more aligned with the NP/PA skill set, or both. In any event, as the scope of hospital medicine broadens, the use of PAs and NPs has also increased – which is probably not coincidental.
The average hospital medicine group continues to have staff openings. Workforce shortages may be leading to what in the past may have been considered physician openings being filled by NPs and PAs. Only 33% of HMGs reported having all their physician openings filled. Median physician shortage was 12% of total approved staffing. Given concerns in hospital medicine about provider burnout, the number of hospital medicine openings is no doubt a concern to HMG leaders and hospitalists. And necessity being the mother of invention, HMG leadership must be thinking differently than in the past about open positions and the skill mix needed to fill them. I believe this is leading to NPs and PAs being considered more often for a role that would have been open only to a physician in the past.
Just as open positions are a concern, so is turnover. One striking finding in the SoHM is the very high rate of turnover among NPs and PAs – a whopping 19.1% per year. For physicians, the same rate was 7.4% and has been declining every survey for many years. While NPs and PAs may be intended to stabilize the workforce, because of how this is being done in some groups, NPs and PAs may instead be a destabilizing factor. Rapid growth can lead to haphazard onboarding and less than clearly defined roles. NPs and PAs may often be placed into roles for which they are not yet prepared. In addition, the pay disparity between NPs and PAs and physicians has increased. As a new field, and with many HMGs still rapidly growing, increased thoughtfulness and maturity about how NPs and PAs are integrated into hospital medicine practices should lead to less turnover and better HMG stability in the future.
These observations could mark a future that includes higher pay for hospital medicine PAs and NPs (and potentially a slowdown in salary growth for physicians); HMGs taking steps to make the financial model more attractive by having NPs and PAs bill independently more often; and HMGs and their leaders engaging NPs and PAs by more clearly defining roles, shoring up onboarding and mentoring programs, and other measures that decrease turnover. This would help to make hospital medicine a career destination, rather than a stopping off point for NPs and PAs, much as it has become for internists over the past 20 years.
Dr. Frederickson is medical director, hospital medicine and palliative care, at CHI Health, Omaha, Neb., and assistant professor at Creighton University, Omaha.