SAN DIEGO – Mental health professionals can lower the risk of legal exposure from patients filing malpractice suits through proper assessment and proper documentation, a psychiatrist said at the annual Psych Congress.

“You don’t have to have a perfect performance, but you do have to gather relevant data. And you’ll be judged on whether you took reasonable precautions once you identified the risk,” said Phillip J. Resnick, MD, professor of psychiatry at Case Western Reserve University, Cleveland.

Research suggests that 35% of malpractice claims involve incorrect treatment and 19% involve medication problems. More than half of all U.S. physicians reportedly have been sued, and psychiatrists are named in lawsuits less often than other medical specialists.

What’s “reasonable” in terms of assessment and precautions? In the past, courts may have held to a community standard: Did you provide the usual care that others in your region would provide? This approach allowed physicians to avoid responsibility if “you could prove that the majority of [local] doctors do what you did,” Dr. Resnick said, even if they’re “sloppy and bad.”

A newer, “reasonably prudent practitioner” standard expects medical professionals to do the right thing no matter where they live. “You have to do what a prudent practitioner would do whether others in your community are doing it or not,” said Dr. Resnick, who has consulted on numerous well-known cases, including that of Jeffrey Dahmer, Susan Smith, Timothy McVey, and Theodore Kaczynski.

Psychiatrists can be vulnerable legally if they refuse to respond to concerns from family members, Dr. Resnick said. The best approach is to listen. “You don’t need permission to listen – only to release information. You can always listen.”

Dr. Resnick is a former president of the American Academy of Psychiatry and the Law. He has no disclosures.

SAN DIEGO – Mental health professionals can lower the risk of legal exposure from patients filing malpractice suits through proper assessment and proper documentation, a psychiatrist said at the annual Psych Congress.

“You don’t have to have a perfect performance, but you do have to gather relevant data. And you’ll be judged on whether you took reasonable precautions once you identified the risk,” said Phillip J. Resnick, MD, professor of psychiatry at Case Western Reserve University, Cleveland.

Research suggests that 35% of malpractice claims involve incorrect treatment and 19% involve medication problems. More than half of all U.S. physicians reportedly have been sued, and psychiatrists are named in lawsuits less often than other medical specialists.

What’s “reasonable” in terms of assessment and precautions? In the past, courts may have held to a community standard: Did you provide the usual care that others in your region would provide? This approach allowed physicians to avoid responsibility if “you could prove that the majority of [local] doctors do what you did,” Dr. Resnick said, even if they’re “sloppy and bad.”

A newer, “reasonably prudent practitioner” standard expects medical professionals to do the right thing no matter where they live. “You have to do what a prudent practitioner would do whether others in your community are doing it or not,” said Dr. Resnick, who has consulted on numerous well-known cases, including that of Jeffrey Dahmer, Susan Smith, Timothy McVey, and Theodore Kaczynski.

Psychiatrists can be vulnerable legally if they refuse to respond to concerns from family members, Dr. Resnick said. The best approach is to listen. “You don’t need permission to listen – only to release information. You can always listen.”

Dr. Resnick is a former president of the American Academy of Psychiatry and the Law. He has no disclosures.

SAN DIEGO – Mental health professionals can lower the risk of legal exposure from patients filing malpractice suits through proper assessment and proper documentation, a psychiatrist said at the annual Psych Congress.

“You don’t have to have a perfect performance, but you do have to gather relevant data. And you’ll be judged on whether you took reasonable precautions once you identified the risk,” said Phillip J. Resnick, MD, professor of psychiatry at Case Western Reserve University, Cleveland.

Research suggests that 35% of malpractice claims involve incorrect treatment and 19% involve medication problems. More than half of all U.S. physicians reportedly have been sued, and psychiatrists are named in lawsuits less often than other medical specialists.

What’s “reasonable” in terms of assessment and precautions? In the past, courts may have held to a community standard: Did you provide the usual care that others in your region would provide? This approach allowed physicians to avoid responsibility if “you could prove that the majority of [local] doctors do what you did,” Dr. Resnick said, even if they’re “sloppy and bad.”

A newer, “reasonably prudent practitioner” standard expects medical professionals to do the right thing no matter where they live. “You have to do what a prudent practitioner would do whether others in your community are doing it or not,” said Dr. Resnick, who has consulted on numerous well-known cases, including that of Jeffrey Dahmer, Susan Smith, Timothy McVey, and Theodore Kaczynski.

Psychiatrists can be vulnerable legally if they refuse to respond to concerns from family members, Dr. Resnick said. The best approach is to listen. “You don’t need permission to listen – only to release information. You can always listen.”

Dr. Resnick is a former president of the American Academy of Psychiatry and the Law. He has no disclosures.

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

marklesney@mdedge.com

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

marklesney@mdedge.com

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

marklesney@mdedge.com

Stray radiation exposure could be responsible for up to 28% of the contralateral breast cancer that occurs years after radiotherapy of the primary tumor.

The risk is highest among women initially treated when younger than 40 years, who had at lest 5 years’ lapse between the first and second occurrences, and had a higher genetic risk score, Gordon P. Watt, PhD, and colleagues reported in JAMA Network Open.

“These findings may support clinical decision making related to radiation treatment, particularly among women for whom other modalities may be considered,” wrote Dr. Watt of Memorial Sloan Kettering Cancer Center, New York, and coauthors. “For example, young women with a high [genetic risk] may consider partial-breast radiation therapy, rather than whole-breast radiation therapy when appropriate, opt for radiation therapy techniques that reduce integral dose (e.g., proton beam), or decide for non–radiation therapy–based locoregional management (e.g., mastectomy). These findings may be especially important in younger women with medially located breast cancers, where the scatter dose to the contralateral breast is likely to be higher.”

The investigators enrolled women who received a diagnosis for a first invasive local or regional breast cancer when they were younger than 55 years in a case-control study to investigate whether the NHEJ genetic risk score (GRS) could predict a woman’s risk of developing contralateral breast cancer after irradiation of a primary breast cancer. The risk score comprises 93 single nucleotide polymorphisms (SNPs) located in or near the seven genes in the NHEJ pathway, including DCLRE1C, LIG4, NHEJ1, PRKDC, XRCC4, XRCC5, and XRCC6. Dr. Watts’ team investigated risks associated with 69 of the SNPs.

The study comprised 3,732 women who were recruited from 2000 to 2012, with primary diagnosis occurring from 1985 to 2008. Of these, 1,521 had contralateral breast cancer; the remainder had unilateral disease and were used as controls.

At first diagnosis, they were aged a median of 46 years, although age ranged from 23 to 54 years. Most of the primary tumors (84%) were ductal. Among the recurrences, 9% were in situ, 63% local, 23% regional, and 2% distant. Stage was unknown on the remainder. Among these recurrent tumors, 54% were estrogen receptor positive and 24% were progesterone receptor positive, with unknown status on the remainder.

For women aged younger than 40 years at the time of the primary tumor, and at least 5 years out from treatment, radiation increased the risk of contralateral disease by 70%. But there was no significant risk to younger women with less than 5 years’ latency, or to women diagnosed at 40 years or older regardless of the time since treatment.

Age played a similar role when considering location-specific stray radiation dose. The risk was doubled in younger women who were exposed to at least 1 Gy and at least 5 years out from treatment, but there was no significantly increased risk to women older at first diagnosis.

Nor were the individual SNPs associated with increased risk. “The NHEJ GRS was approximately normally distributed and was dichotomized at the overall median for analysis; the median (range) GRS in the case group was 75 alleles and the median GRS in the control group was 74 alleles,” the investigators wrote.

But when examined by total GRS score, differences emerged.

“In the high NHEJ GRS group, among women who received the first diagnosis when they were younger than 40 years with a latency of 5 years or more, a stray radiation dose of 1.0 Gy or more was associated with threefold greater contralateral breast cancer risk, compared with no radiation exposure. In contrast, for women with an NHEJ GRS of 74 alleles or fewer in the same age and latency group, there was no association between radiation dose and contralateral breast cancer,” they wrote.

Again, there was no increased risk for women aged older than 40 years at first diagnosis.

“Based on these results, after a latency of 5 years or longer among women who received their first breast cancer diagnosis when they were younger than 40 years with a high NHEJ GRS, the population-attributable risk fraction of contralateral breast cancer attributable to stray radiation exposure to the contralateral breast was 28%. The corresponding population attributable risk fraction among women who received their first diagnosis when they were younger than 40 years after a latency of 5 years or more with a low NHEJ GRS was 18%,” the investigators wrote.

Five of the seven NHEJ pathway genes appeared to be driving these increased risks: LIG4, NHEJ1, XRCC4, XRCC5, and XRCC6. The expression quantitative trait loci (eQTLs) in each gene were always associated with a single direction of association; all risk alleles in XRCC4 were associated with decreased expression and all risk alleles in LIG4 were associated with increased expression.

“The consistent association of multiple NHEJ GRS risk alleles with eQTLs in a single direction suggests that the NHEJ GRS may be capturing the effect of SNP alleles on the transcription of one or more genes in the NHEJ pathway. This supports the hypothesis that the variation in this pathway may alter double-stranded DNA damage response, thereby increasing the risk of tumor development. However, the results from [the Genotype-Tissue Expression database] are drawn from multiple tissues that may not be appropriate proxies for breast tissue and the impact of genetic variation in the overall NHEJ pathway is likely to be complex,” the investigators wrote.

Dr. Watt had no financial disclosures. The research was funded by the National Cancer Institute.

SOURCE: Watt GP et al. JAMA Netw Open. 2019 Sep 27. doi: 10.1001/jamanetworkopen.2019.12259.

Stray radiation exposure could be responsible for up to 28% of the contralateral breast cancer that occurs years after radiotherapy of the primary tumor.

The risk is highest among women initially treated when younger than 40 years, who had at lest 5 years’ lapse between the first and second occurrences, and had a higher genetic risk score, Gordon P. Watt, PhD, and colleagues reported in JAMA Network Open.

“These findings may support clinical decision making related to radiation treatment, particularly among women for whom other modalities may be considered,” wrote Dr. Watt of Memorial Sloan Kettering Cancer Center, New York, and coauthors. “For example, young women with a high [genetic risk] may consider partial-breast radiation therapy, rather than whole-breast radiation therapy when appropriate, opt for radiation therapy techniques that reduce integral dose (e.g., proton beam), or decide for non–radiation therapy–based locoregional management (e.g., mastectomy). These findings may be especially important in younger women with medially located breast cancers, where the scatter dose to the contralateral breast is likely to be higher.”

The investigators enrolled women who received a diagnosis for a first invasive local or regional breast cancer when they were younger than 55 years in a case-control study to investigate whether the NHEJ genetic risk score (GRS) could predict a woman’s risk of developing contralateral breast cancer after irradiation of a primary breast cancer. The risk score comprises 93 single nucleotide polymorphisms (SNPs) located in or near the seven genes in the NHEJ pathway, including DCLRE1C, LIG4, NHEJ1, PRKDC, XRCC4, XRCC5, and XRCC6. Dr. Watts’ team investigated risks associated with 69 of the SNPs.

The study comprised 3,732 women who were recruited from 2000 to 2012, with primary diagnosis occurring from 1985 to 2008. Of these, 1,521 had contralateral breast cancer; the remainder had unilateral disease and were used as controls.

At first diagnosis, they were aged a median of 46 years, although age ranged from 23 to 54 years. Most of the primary tumors (84%) were ductal. Among the recurrences, 9% were in situ, 63% local, 23% regional, and 2% distant. Stage was unknown on the remainder. Among these recurrent tumors, 54% were estrogen receptor positive and 24% were progesterone receptor positive, with unknown status on the remainder.

For women aged younger than 40 years at the time of the primary tumor, and at least 5 years out from treatment, radiation increased the risk of contralateral disease by 70%. But there was no significant risk to younger women with less than 5 years’ latency, or to women diagnosed at 40 years or older regardless of the time since treatment.

Age played a similar role when considering location-specific stray radiation dose. The risk was doubled in younger women who were exposed to at least 1 Gy and at least 5 years out from treatment, but there was no significantly increased risk to women older at first diagnosis.

Nor were the individual SNPs associated with increased risk. “The NHEJ GRS was approximately normally distributed and was dichotomized at the overall median for analysis; the median (range) GRS in the case group was 75 alleles and the median GRS in the control group was 74 alleles,” the investigators wrote.

But when examined by total GRS score, differences emerged.

“In the high NHEJ GRS group, among women who received the first diagnosis when they were younger than 40 years with a latency of 5 years or more, a stray radiation dose of 1.0 Gy or more was associated with threefold greater contralateral breast cancer risk, compared with no radiation exposure. In contrast, for women with an NHEJ GRS of 74 alleles or fewer in the same age and latency group, there was no association between radiation dose and contralateral breast cancer,” they wrote.

Again, there was no increased risk for women aged older than 40 years at first diagnosis.

“Based on these results, after a latency of 5 years or longer among women who received their first breast cancer diagnosis when they were younger than 40 years with a high NHEJ GRS, the population-attributable risk fraction of contralateral breast cancer attributable to stray radiation exposure to the contralateral breast was 28%. The corresponding population attributable risk fraction among women who received their first diagnosis when they were younger than 40 years after a latency of 5 years or more with a low NHEJ GRS was 18%,” the investigators wrote.

Five of the seven NHEJ pathway genes appeared to be driving these increased risks: LIG4, NHEJ1, XRCC4, XRCC5, and XRCC6. The expression quantitative trait loci (eQTLs) in each gene were always associated with a single direction of association; all risk alleles in XRCC4 were associated with decreased expression and all risk alleles in LIG4 were associated with increased expression.

“The consistent association of multiple NHEJ GRS risk alleles with eQTLs in a single direction suggests that the NHEJ GRS may be capturing the effect of SNP alleles on the transcription of one or more genes in the NHEJ pathway. This supports the hypothesis that the variation in this pathway may alter double-stranded DNA damage response, thereby increasing the risk of tumor development. However, the results from [the Genotype-Tissue Expression database] are drawn from multiple tissues that may not be appropriate proxies for breast tissue and the impact of genetic variation in the overall NHEJ pathway is likely to be complex,” the investigators wrote.

Dr. Watt had no financial disclosures. The research was funded by the National Cancer Institute.

SOURCE: Watt GP et al. JAMA Netw Open. 2019 Sep 27. doi: 10.1001/jamanetworkopen.2019.12259.

Stray radiation exposure could be responsible for up to 28% of the contralateral breast cancer that occurs years after radiotherapy of the primary tumor.

The risk is highest among women initially treated when younger than 40 years, who had at lest 5 years’ lapse between the first and second occurrences, and had a higher genetic risk score, Gordon P. Watt, PhD, and colleagues reported in JAMA Network Open.

“These findings may support clinical decision making related to radiation treatment, particularly among women for whom other modalities may be considered,” wrote Dr. Watt of Memorial Sloan Kettering Cancer Center, New York, and coauthors. “For example, young women with a high [genetic risk] may consider partial-breast radiation therapy, rather than whole-breast radiation therapy when appropriate, opt for radiation therapy techniques that reduce integral dose (e.g., proton beam), or decide for non–radiation therapy–based locoregional management (e.g., mastectomy). These findings may be especially important in younger women with medially located breast cancers, where the scatter dose to the contralateral breast is likely to be higher.”

The investigators enrolled women who received a diagnosis for a first invasive local or regional breast cancer when they were younger than 55 years in a case-control study to investigate whether the NHEJ genetic risk score (GRS) could predict a woman’s risk of developing contralateral breast cancer after irradiation of a primary breast cancer. The risk score comprises 93 single nucleotide polymorphisms (SNPs) located in or near the seven genes in the NHEJ pathway, including DCLRE1C, LIG4, NHEJ1, PRKDC, XRCC4, XRCC5, and XRCC6. Dr. Watts’ team investigated risks associated with 69 of the SNPs.

The study comprised 3,732 women who were recruited from 2000 to 2012, with primary diagnosis occurring from 1985 to 2008. Of these, 1,521 had contralateral breast cancer; the remainder had unilateral disease and were used as controls.

At first diagnosis, they were aged a median of 46 years, although age ranged from 23 to 54 years. Most of the primary tumors (84%) were ductal. Among the recurrences, 9% were in situ, 63% local, 23% regional, and 2% distant. Stage was unknown on the remainder. Among these recurrent tumors, 54% were estrogen receptor positive and 24% were progesterone receptor positive, with unknown status on the remainder.

For women aged younger than 40 years at the time of the primary tumor, and at least 5 years out from treatment, radiation increased the risk of contralateral disease by 70%. But there was no significant risk to younger women with less than 5 years’ latency, or to women diagnosed at 40 years or older regardless of the time since treatment.

Age played a similar role when considering location-specific stray radiation dose. The risk was doubled in younger women who were exposed to at least 1 Gy and at least 5 years out from treatment, but there was no significantly increased risk to women older at first diagnosis.

Nor were the individual SNPs associated with increased risk. “The NHEJ GRS was approximately normally distributed and was dichotomized at the overall median for analysis; the median (range) GRS in the case group was 75 alleles and the median GRS in the control group was 74 alleles,” the investigators wrote.

But when examined by total GRS score, differences emerged.

“In the high NHEJ GRS group, among women who received the first diagnosis when they were younger than 40 years with a latency of 5 years or more, a stray radiation dose of 1.0 Gy or more was associated with threefold greater contralateral breast cancer risk, compared with no radiation exposure. In contrast, for women with an NHEJ GRS of 74 alleles or fewer in the same age and latency group, there was no association between radiation dose and contralateral breast cancer,” they wrote.

Again, there was no increased risk for women aged older than 40 years at first diagnosis.

“Based on these results, after a latency of 5 years or longer among women who received their first breast cancer diagnosis when they were younger than 40 years with a high NHEJ GRS, the population-attributable risk fraction of contralateral breast cancer attributable to stray radiation exposure to the contralateral breast was 28%. The corresponding population attributable risk fraction among women who received their first diagnosis when they were younger than 40 years after a latency of 5 years or more with a low NHEJ GRS was 18%,” the investigators wrote.

Five of the seven NHEJ pathway genes appeared to be driving these increased risks: LIG4, NHEJ1, XRCC4, XRCC5, and XRCC6. The expression quantitative trait loci (eQTLs) in each gene were always associated with a single direction of association; all risk alleles in XRCC4 were associated with decreased expression and all risk alleles in LIG4 were associated with increased expression.

“The consistent association of multiple NHEJ GRS risk alleles with eQTLs in a single direction suggests that the NHEJ GRS may be capturing the effect of SNP alleles on the transcription of one or more genes in the NHEJ pathway. This supports the hypothesis that the variation in this pathway may alter double-stranded DNA damage response, thereby increasing the risk of tumor development. However, the results from [the Genotype-Tissue Expression database] are drawn from multiple tissues that may not be appropriate proxies for breast tissue and the impact of genetic variation in the overall NHEJ pathway is likely to be complex,” the investigators wrote.

Dr. Watt had no financial disclosures. The research was funded by the National Cancer Institute.

SOURCE: Watt GP et al. JAMA Netw Open. 2019 Sep 27. doi: 10.1001/jamanetworkopen.2019.12259.

SAN DIEGO – Substance use disorders rarely ride alone, a psychiatrist told colleagues, and it’s crucial to treat the accompanying mental illness that is almost always present.

“If you’re really depressed and you’re smoking marijuana, the smoking could have made it worse, but you were probably depressed before,” said Timothy E. Wilens, MD, of Harvard Medical School and Massachusetts General Hospital, both in Boston. Dr. Wilens spoke at the annual Psych Congress.

He pointed to numbers supporting the link between substance use and mental illness. He also offered several tips about treating substance use disorder (SUD).

In ADHD, consider the big picture. If a person has both ADHD and SUD, treat both if the level of substance abuse is lower. But focus on the SUD in more severe cases, he said, and realize that “most likely your treatment for ADHD isn’t going to work as well.”

Be prepared to give high doses. “When you’re using stimulants in people with use disorders, you have to use high doses. You have to be brave,” he said. The same goes for the anxiolytic buspirone (Buspar) in patients with depression and SUD.

Consider N-acetyl cysteine in cannabis use disorder. N-acetyl cysteine, a nutraceutical used as an asthma medication, has shown promise in trials as a treatment for cannabis use disorder, Dr. Wilens said. It helps patients avoid the temptation to smoke. “They won’t say they’ve lost all their cravings, but you’ll hear, ‘I just didn’t need to do it; I’m not smoking as much.’ If you hear that from your patients, you know it’s working. It’s a subtle effect, but it can help.”

Scamming’ drugs shouldn’t be your main worry. Substance use research suggests that users of pharmaceutical drugs for nonmedical uses rarely get them directly from practitioners (7%), but instead mainly get them through friends, Dr. Wilens said. “If you work with this population and treat ADHD or anxiety, you’re paranoid that everyone coming in wants to scam medicines. Be more concerned about oversupplying them with immediate-release medications and not [taking] them to task about keeping the medication safely stored.”

Interventions such as Alcoholics Anonymous are as “effective as any other treatment for substance abuse, and it’s not costly,” Dr. Wilens said. He added that the Rational Recovery program, an alternative to Alcoholics Anonymous, also seems to work well. The approaches to ending substance use differ in that Alcoholics Anonymous’s orientation is spiritual and Rational Recovery’s is cognitive.

Dr. Wilens reported various disclosures, including consulting relationships with Ironshore Pharmaceuticals, KemPharm, and Neurovance/Otsuka.

SAN DIEGO – Substance use disorders rarely ride alone, a psychiatrist told colleagues, and it’s crucial to treat the accompanying mental illness that is almost always present.

“If you’re really depressed and you’re smoking marijuana, the smoking could have made it worse, but you were probably depressed before,” said Timothy E. Wilens, MD, of Harvard Medical School and Massachusetts General Hospital, both in Boston. Dr. Wilens spoke at the annual Psych Congress.

He pointed to numbers supporting the link between substance use and mental illness. He also offered several tips about treating substance use disorder (SUD).

In ADHD, consider the big picture. If a person has both ADHD and SUD, treat both if the level of substance abuse is lower. But focus on the SUD in more severe cases, he said, and realize that “most likely your treatment for ADHD isn’t going to work as well.”

Be prepared to give high doses. “When you’re using stimulants in people with use disorders, you have to use high doses. You have to be brave,” he said. The same goes for the anxiolytic buspirone (Buspar) in patients with depression and SUD.

Consider N-acetyl cysteine in cannabis use disorder. N-acetyl cysteine, a nutraceutical used as an asthma medication, has shown promise in trials as a treatment for cannabis use disorder, Dr. Wilens said. It helps patients avoid the temptation to smoke. “They won’t say they’ve lost all their cravings, but you’ll hear, ‘I just didn’t need to do it; I’m not smoking as much.’ If you hear that from your patients, you know it’s working. It’s a subtle effect, but it can help.”

Scamming’ drugs shouldn’t be your main worry. Substance use research suggests that users of pharmaceutical drugs for nonmedical uses rarely get them directly from practitioners (7%), but instead mainly get them through friends, Dr. Wilens said. “If you work with this population and treat ADHD or anxiety, you’re paranoid that everyone coming in wants to scam medicines. Be more concerned about oversupplying them with immediate-release medications and not [taking] them to task about keeping the medication safely stored.”

Interventions such as Alcoholics Anonymous are as “effective as any other treatment for substance abuse, and it’s not costly,” Dr. Wilens said. He added that the Rational Recovery program, an alternative to Alcoholics Anonymous, also seems to work well. The approaches to ending substance use differ in that Alcoholics Anonymous’s orientation is spiritual and Rational Recovery’s is cognitive.

Dr. Wilens reported various disclosures, including consulting relationships with Ironshore Pharmaceuticals, KemPharm, and Neurovance/Otsuka.

SAN DIEGO – Substance use disorders rarely ride alone, a psychiatrist told colleagues, and it’s crucial to treat the accompanying mental illness that is almost always present.

“If you’re really depressed and you’re smoking marijuana, the smoking could have made it worse, but you were probably depressed before,” said Timothy E. Wilens, MD, of Harvard Medical School and Massachusetts General Hospital, both in Boston. Dr. Wilens spoke at the annual Psych Congress.

He pointed to numbers supporting the link between substance use and mental illness. He also offered several tips about treating substance use disorder (SUD).

In ADHD, consider the big picture. If a person has both ADHD and SUD, treat both if the level of substance abuse is lower. But focus on the SUD in more severe cases, he said, and realize that “most likely your treatment for ADHD isn’t going to work as well.”

Be prepared to give high doses. “When you’re using stimulants in people with use disorders, you have to use high doses. You have to be brave,” he said. The same goes for the anxiolytic buspirone (Buspar) in patients with depression and SUD.

Consider N-acetyl cysteine in cannabis use disorder. N-acetyl cysteine, a nutraceutical used as an asthma medication, has shown promise in trials as a treatment for cannabis use disorder, Dr. Wilens said. It helps patients avoid the temptation to smoke. “They won’t say they’ve lost all their cravings, but you’ll hear, ‘I just didn’t need to do it; I’m not smoking as much.’ If you hear that from your patients, you know it’s working. It’s a subtle effect, but it can help.”

Scamming’ drugs shouldn’t be your main worry. Substance use research suggests that users of pharmaceutical drugs for nonmedical uses rarely get them directly from practitioners (7%), but instead mainly get them through friends, Dr. Wilens said. “If you work with this population and treat ADHD or anxiety, you’re paranoid that everyone coming in wants to scam medicines. Be more concerned about oversupplying them with immediate-release medications and not [taking] them to task about keeping the medication safely stored.”

Interventions such as Alcoholics Anonymous are as “effective as any other treatment for substance abuse, and it’s not costly,” Dr. Wilens said. He added that the Rational Recovery program, an alternative to Alcoholics Anonymous, also seems to work well. The approaches to ending substance use differ in that Alcoholics Anonymous’s orientation is spiritual and Rational Recovery’s is cognitive.

Dr. Wilens reported various disclosures, including consulting relationships with Ironshore Pharmaceuticals, KemPharm, and Neurovance/Otsuka.

It with sadness that I read the new Department of Defense report documenting an increasing number of suicides in the military. And also, cynicism about the proposed remedies.

According the DoD report, the rate of suicide among active-duty military increased from 18.5 per 100,000 service members in 2013 to 24.8 suicides per service members in 2018.

For context, I was in the Army for a career and at the office of the Army surgeon general from 2005 to 2010. That was when the suicide rate began to rise from the normal 10 per 100,000 soldiers per year to almost double that rate.

I led conferences within the Army Medical Command aimed at reducing suicides. Later, when the problem escalated, I participated in a variety of efforts to lower it. I went to Iraq to consult.

There was a Department of the Army task force on suicide prevention. Later, a DoD task force.

Numerous recommendations were made. If I remember right, the Army task force had almost 200 recommendations. They ranged from tightening accession standards, to providing more mental health care. The issues of shaming and blaming commanders also were a key topic of discussion.

Resiliency training was big. At some point, there were more than 200 resilience programs in the DoD. There were no data (to my knowledge) showing that they work.

An emphasis was the message: “It is a sign of strength to ask for help.”

For a while, the suicide rate flattened among active-duty soldiers, although the rate continued to climb among National Guard and reservists.

The solutions were similar to those proposed in this article. The leaders in the Army and DoD were not shy about asking for help. The Army Study to Assess Risk and Resilience in Servicemembers (STARRS) program was created to examine risk factors for suicide.

The STARRS program had data to show us what we already knew. The majority of suicides are in young, enlisted men with access to firearms. Often, but not always, they had a history of suicide ideation or attempts.

The trigger was usually, but not always, precipitated by a humiliating event, such as breaking up with a partner, driving while intoxicated, or getting in trouble at work.

Now, almost 10 years into retirement from the military, I feel sorry for my former colleagues. They have tried everything they can think of.

One solution, which is out of the control of military mental health workers, is to limit access to guns. Consistently, about two-thirds of suicides in the military are by gunshot.

So, as we continue to look for ways to bring an end to these losses, we must not blame the military. After all, they have tried all they can think of. However, I can think of one factor we can blame: the all-too-easy access to firearms.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

It with sadness that I read the new Department of Defense report documenting an increasing number of suicides in the military. And also, cynicism about the proposed remedies.

According the DoD report, the rate of suicide among active-duty military increased from 18.5 per 100,000 service members in 2013 to 24.8 suicides per service members in 2018.

For context, I was in the Army for a career and at the office of the Army surgeon general from 2005 to 2010. That was when the suicide rate began to rise from the normal 10 per 100,000 soldiers per year to almost double that rate.

I led conferences within the Army Medical Command aimed at reducing suicides. Later, when the problem escalated, I participated in a variety of efforts to lower it. I went to Iraq to consult.

There was a Department of the Army task force on suicide prevention. Later, a DoD task force.

Numerous recommendations were made. If I remember right, the Army task force had almost 200 recommendations. They ranged from tightening accession standards, to providing more mental health care. The issues of shaming and blaming commanders also were a key topic of discussion.

Resiliency training was big. At some point, there were more than 200 resilience programs in the DoD. There were no data (to my knowledge) showing that they work.

An emphasis was the message: “It is a sign of strength to ask for help.”

For a while, the suicide rate flattened among active-duty soldiers, although the rate continued to climb among National Guard and reservists.

The solutions were similar to those proposed in this article. The leaders in the Army and DoD were not shy about asking for help. The Army Study to Assess Risk and Resilience in Servicemembers (STARRS) program was created to examine risk factors for suicide.

The STARRS program had data to show us what we already knew. The majority of suicides are in young, enlisted men with access to firearms. Often, but not always, they had a history of suicide ideation or attempts.

The trigger was usually, but not always, precipitated by a humiliating event, such as breaking up with a partner, driving while intoxicated, or getting in trouble at work.

Now, almost 10 years into retirement from the military, I feel sorry for my former colleagues. They have tried everything they can think of.

One solution, which is out of the control of military mental health workers, is to limit access to guns. Consistently, about two-thirds of suicides in the military are by gunshot.

So, as we continue to look for ways to bring an end to these losses, we must not blame the military. After all, they have tried all they can think of. However, I can think of one factor we can blame: the all-too-easy access to firearms.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

It with sadness that I read the new Department of Defense report documenting an increasing number of suicides in the military. And also, cynicism about the proposed remedies.

According the DoD report, the rate of suicide among active-duty military increased from 18.5 per 100,000 service members in 2013 to 24.8 suicides per service members in 2018.

For context, I was in the Army for a career and at the office of the Army surgeon general from 2005 to 2010. That was when the suicide rate began to rise from the normal 10 per 100,000 soldiers per year to almost double that rate.

I led conferences within the Army Medical Command aimed at reducing suicides. Later, when the problem escalated, I participated in a variety of efforts to lower it. I went to Iraq to consult.

There was a Department of the Army task force on suicide prevention. Later, a DoD task force.

Numerous recommendations were made. If I remember right, the Army task force had almost 200 recommendations. They ranged from tightening accession standards, to providing more mental health care. The issues of shaming and blaming commanders also were a key topic of discussion.

Resiliency training was big. At some point, there were more than 200 resilience programs in the DoD. There were no data (to my knowledge) showing that they work.

An emphasis was the message: “It is a sign of strength to ask for help.”

For a while, the suicide rate flattened among active-duty soldiers, although the rate continued to climb among National Guard and reservists.

The solutions were similar to those proposed in this article. The leaders in the Army and DoD were not shy about asking for help. The Army Study to Assess Risk and Resilience in Servicemembers (STARRS) program was created to examine risk factors for suicide.

The STARRS program had data to show us what we already knew. The majority of suicides are in young, enlisted men with access to firearms. Often, but not always, they had a history of suicide ideation or attempts.

The trigger was usually, but not always, precipitated by a humiliating event, such as breaking up with a partner, driving while intoxicated, or getting in trouble at work.

Now, almost 10 years into retirement from the military, I feel sorry for my former colleagues. They have tried everything they can think of.

One solution, which is out of the control of military mental health workers, is to limit access to guns. Consistently, about two-thirds of suicides in the military are by gunshot.

So, as we continue to look for ways to bring an end to these losses, we must not blame the military. After all, they have tried all they can think of. However, I can think of one factor we can blame: the all-too-easy access to firearms.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

SAN DIEGO – A relatively new treatment approach called good psychiatric management (GPM) is available for patients with borderline personality disorder.

It’s a solid option for “environments where people may not have many resources and might not be able to deliver treatments that are more resource intensive, like dialectical behavioral therapy,” the standard intervention, said James Jenkins, MD, a psychiatrist affiliated with Massachusetts General Hospital, Boston, in a video interview at the annual Psych Congress.

“GPM is a treatment, not a psychotherapy, that’s maybe a little bit more easily adaptable to a variety of different contexts and situations,” he said.

It’s an atheoretical, pragmatic approach that focuses on helping people establish a life outside of therapy. Clinicians actively engage with patients, encouraging them to start working and building successful relationships with other people. The model emphasizes the value of educating people about the condition and giving them hope. Typically, patients participate in GPM once each week (Curr Opin Psychol. 2018 Jun;21:127-31).

Vidyard Video

For most people, it works just as well as dialectical behavioral therapy, and when it doesn’t, patients can transition to that or another more intensive approach. Training is less intensive and sometimes free. GPM is offered at McLean Hospital in Boston, where the intervention originated. McLean also is Dr. Jenkins’s former institution.

Dr. Jenkins reported that he had no disclosures.

aotto@mdedge.com

SAN DIEGO – A relatively new treatment approach called good psychiatric management (GPM) is available for patients with borderline personality disorder.

It’s a solid option for “environments where people may not have many resources and might not be able to deliver treatments that are more resource intensive, like dialectical behavioral therapy,” the standard intervention, said James Jenkins, MD, a psychiatrist affiliated with Massachusetts General Hospital, Boston, in a video interview at the annual Psych Congress.

“GPM is a treatment, not a psychotherapy, that’s maybe a little bit more easily adaptable to a variety of different contexts and situations,” he said.

It’s an atheoretical, pragmatic approach that focuses on helping people establish a life outside of therapy. Clinicians actively engage with patients, encouraging them to start working and building successful relationships with other people. The model emphasizes the value of educating people about the condition and giving them hope. Typically, patients participate in GPM once each week (Curr Opin Psychol. 2018 Jun;21:127-31).

Vidyard Video

For most people, it works just as well as dialectical behavioral therapy, and when it doesn’t, patients can transition to that or another more intensive approach. Training is less intensive and sometimes free. GPM is offered at McLean Hospital in Boston, where the intervention originated. McLean also is Dr. Jenkins’s former institution.

Dr. Jenkins reported that he had no disclosures.

aotto@mdedge.com

SAN DIEGO – A relatively new treatment approach called good psychiatric management (GPM) is available for patients with borderline personality disorder.

It’s a solid option for “environments where people may not have many resources and might not be able to deliver treatments that are more resource intensive, like dialectical behavioral therapy,” the standard intervention, said James Jenkins, MD, a psychiatrist affiliated with Massachusetts General Hospital, Boston, in a video interview at the annual Psych Congress.

“GPM is a treatment, not a psychotherapy, that’s maybe a little bit more easily adaptable to a variety of different contexts and situations,” he said.

It’s an atheoretical, pragmatic approach that focuses on helping people establish a life outside of therapy. Clinicians actively engage with patients, encouraging them to start working and building successful relationships with other people. The model emphasizes the value of educating people about the condition and giving them hope. Typically, patients participate in GPM once each week (Curr Opin Psychol. 2018 Jun;21:127-31).

Vidyard Video

For most people, it works just as well as dialectical behavioral therapy, and when it doesn’t, patients can transition to that or another more intensive approach. Training is less intensive and sometimes free. GPM is offered at McLean Hospital in Boston, where the intervention originated. McLean also is Dr. Jenkins’s former institution.

Dr. Jenkins reported that he had no disclosures.

aotto@mdedge.com

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

SAN DIEGO – While an “exciting” ketamine-based product is finally available and approved to treat treatment-resistant depression (TRD), there are still plenty of questions about the use of intranasal esketamine, a psychiatrist told colleagues.

“We have a lot of unmet needs in terms of research,” said Sanjay J. Mathew, MD, of Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, both in Houston, at the annual Psych Congress. “What do we do in the long term? What are the dosing strategies and response predictors? What about elderly patients?”

The Food and Drug Administration approved esketamine nasal spray (Spravato) for TRD in March 2019. Patients with TRD are defined as those with major depressive disorder who have failed at least two different antidepressants.

Dr. Mathew highlighted a 2019 randomized, double-blind, controlled study of patients who reached stable remission after 16 weeks on esketamine. It revealed there’s “a significant enhancement of the time to relapse for patients who remained on ketamine [compared with placebo] – a 51% risk reduction in the median number of days to relapse” (JAMA Psychiatry. 2019;76[9]:893-903).

However, about a quarter of patients still relapsed over the time of the study, Dr. Mathew said. “While this is certainly exciting, we need to talk to our patients about this and set expectations. And we need to emphasize close vigilance, follow-up, and psychotherapy.”

Patients should understand that, if patients are doing remarkably well at 16 weeks, “you’re not out of the woods. You really need to take it long term,” he said.

Dr. Mathew emphasized that patients must take the drug under supervision in a certified facility. “It’s a quick and simple process to do it [get certified] and get registered,” he said. Patients must be monitored over 2 hours and not drive for the rest of the day.

“You need space for some privacy, so a busy [postanesthesia care unit] or ER setting may not be optimal,” he said, adding that, “if you only have one office, it’s hard to pull this off for a number of logistical reasons.”

Dr. Mathew recommended lowering the level of stimulation in the room where the drug is administered. “We have a VA setting that can be loud with code greens blasting over the speaker,” he said. “That is not optimal, but at least we have a private room for our IV infusions. Keep the lights muted, let the patient listen to peaceful music that they enjoy. Having a family member close by can be helpful and comforting to them.”

He added that “you do need a way to recline the head. Having a barber-type chair would be necessary.”

Side effects are common, he said. Sedation is a major risk (49%-61%), as is dissociation (61%-75%). “It’s primarily a sense of alteration – perceptual alterations, altered sense of time, unreality, being disconnected from body, feeling unusually big in fingers or hands, or feeling like you’re unusually tall or skinny.”

Moving forward, more data about long-term effects and ideal doses are needed. “There are many clinics that go above 0.5 milligrams per kg, and some even go to 2. We have no good data,” he said.

People aged over 65 years have lower response rates, and men seem to respond less than women. Dr. Mathew also noted that the studies into the drug generally limited the number of antidepressant failures in patients: “Are there patients too refractory to be considered for this? How refractory is too refractory?”

Dr. Mathew reported various disclosures including a relationship with Janssen, manufacturer of intranasal esketamine.

SAN DIEGO – While an “exciting” ketamine-based product is finally available and approved to treat treatment-resistant depression (TRD), there are still plenty of questions about the use of intranasal esketamine, a psychiatrist told colleagues.

“We have a lot of unmet needs in terms of research,” said Sanjay J. Mathew, MD, of Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, both in Houston, at the annual Psych Congress. “What do we do in the long term? What are the dosing strategies and response predictors? What about elderly patients?”

The Food and Drug Administration approved esketamine nasal spray (Spravato) for TRD in March 2019. Patients with TRD are defined as those with major depressive disorder who have failed at least two different antidepressants.

Dr. Mathew highlighted a 2019 randomized, double-blind, controlled study of patients who reached stable remission after 16 weeks on esketamine. It revealed there’s “a significant enhancement of the time to relapse for patients who remained on ketamine [compared with placebo] – a 51% risk reduction in the median number of days to relapse” (JAMA Psychiatry. 2019;76[9]:893-903).

However, about a quarter of patients still relapsed over the time of the study, Dr. Mathew said. “While this is certainly exciting, we need to talk to our patients about this and set expectations. And we need to emphasize close vigilance, follow-up, and psychotherapy.”

Patients should understand that, if patients are doing remarkably well at 16 weeks, “you’re not out of the woods. You really need to take it long term,” he said.

Dr. Mathew emphasized that patients must take the drug under supervision in a certified facility. “It’s a quick and simple process to do it [get certified] and get registered,” he said. Patients must be monitored over 2 hours and not drive for the rest of the day.

“You need space for some privacy, so a busy [postanesthesia care unit] or ER setting may not be optimal,” he said, adding that, “if you only have one office, it’s hard to pull this off for a number of logistical reasons.”

Dr. Mathew recommended lowering the level of stimulation in the room where the drug is administered. “We have a VA setting that can be loud with code greens blasting over the speaker,” he said. “That is not optimal, but at least we have a private room for our IV infusions. Keep the lights muted, let the patient listen to peaceful music that they enjoy. Having a family member close by can be helpful and comforting to them.”

He added that “you do need a way to recline the head. Having a barber-type chair would be necessary.”

Side effects are common, he said. Sedation is a major risk (49%-61%), as is dissociation (61%-75%). “It’s primarily a sense of alteration – perceptual alterations, altered sense of time, unreality, being disconnected from body, feeling unusually big in fingers or hands, or feeling like you’re unusually tall or skinny.”

Moving forward, more data about long-term effects and ideal doses are needed. “There are many clinics that go above 0.5 milligrams per kg, and some even go to 2. We have no good data,” he said.

People aged over 65 years have lower response rates, and men seem to respond less than women. Dr. Mathew also noted that the studies into the drug generally limited the number of antidepressant failures in patients: “Are there patients too refractory to be considered for this? How refractory is too refractory?”

Dr. Mathew reported various disclosures including a relationship with Janssen, manufacturer of intranasal esketamine.

SAN DIEGO – While an “exciting” ketamine-based product is finally available and approved to treat treatment-resistant depression (TRD), there are still plenty of questions about the use of intranasal esketamine, a psychiatrist told colleagues.

“We have a lot of unmet needs in terms of research,” said Sanjay J. Mathew, MD, of Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, both in Houston, at the annual Psych Congress. “What do we do in the long term? What are the dosing strategies and response predictors? What about elderly patients?”

The Food and Drug Administration approved esketamine nasal spray (Spravato) for TRD in March 2019. Patients with TRD are defined as those with major depressive disorder who have failed at least two different antidepressants.

Dr. Mathew highlighted a 2019 randomized, double-blind, controlled study of patients who reached stable remission after 16 weeks on esketamine. It revealed there’s “a significant enhancement of the time to relapse for patients who remained on ketamine [compared with placebo] – a 51% risk reduction in the median number of days to relapse” (JAMA Psychiatry. 2019;76[9]:893-903).

However, about a quarter of patients still relapsed over the time of the study, Dr. Mathew said. “While this is certainly exciting, we need to talk to our patients about this and set expectations. And we need to emphasize close vigilance, follow-up, and psychotherapy.”

Patients should understand that, if patients are doing remarkably well at 16 weeks, “you’re not out of the woods. You really need to take it long term,” he said.

Dr. Mathew emphasized that patients must take the drug under supervision in a certified facility. “It’s a quick and simple process to do it [get certified] and get registered,” he said. Patients must be monitored over 2 hours and not drive for the rest of the day.

“You need space for some privacy, so a busy [postanesthesia care unit] or ER setting may not be optimal,” he said, adding that, “if you only have one office, it’s hard to pull this off for a number of logistical reasons.”

Dr. Mathew recommended lowering the level of stimulation in the room where the drug is administered. “We have a VA setting that can be loud with code greens blasting over the speaker,” he said. “That is not optimal, but at least we have a private room for our IV infusions. Keep the lights muted, let the patient listen to peaceful music that they enjoy. Having a family member close by can be helpful and comforting to them.”

He added that “you do need a way to recline the head. Having a barber-type chair would be necessary.”

Side effects are common, he said. Sedation is a major risk (49%-61%), as is dissociation (61%-75%). “It’s primarily a sense of alteration – perceptual alterations, altered sense of time, unreality, being disconnected from body, feeling unusually big in fingers or hands, or feeling like you’re unusually tall or skinny.”

Moving forward, more data about long-term effects and ideal doses are needed. “There are many clinics that go above 0.5 milligrams per kg, and some even go to 2. We have no good data,” he said.

People aged over 65 years have lower response rates, and men seem to respond less than women. Dr. Mathew also noted that the studies into the drug generally limited the number of antidepressant failures in patients: “Are there patients too refractory to be considered for this? How refractory is too refractory?”

Dr. Mathew reported various disclosures including a relationship with Janssen, manufacturer of intranasal esketamine.