Federal Practitioner

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

Hepatocellular carcinoma (HCC) is relatively common among patients with alcohol-associated cirrhosis, reaching a cumulative incidence of 9% at the 10-year mark, shows a large pooled analysis.

Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.

National University of Singapore

“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.

Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.

To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.

“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”

The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.

“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”

The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).

“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.

Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.

Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.

Hepatocellular carcinoma (HCC) is relatively common among patients with alcohol-associated cirrhosis, reaching a cumulative incidence of 9% at the 10-year mark, shows a large pooled analysis.

Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.

National University of Singapore

“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.

Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.

To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.

“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”

The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.

“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”

The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).

“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.

Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.

Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.

Hepatocellular carcinoma (HCC) is relatively common among patients with alcohol-associated cirrhosis, reaching a cumulative incidence of 9% at the 10-year mark, shows a large pooled analysis.

Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.

National University of Singapore

“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.

Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.

To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.

“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”

The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.

“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”

The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).

“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.

Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.

Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – As the study of cutaneous dysbiosis and its role in the pathogenesis of dermatoses continues to evolve, how the mounting evidence on this topic translates into clinical practice remains largely unknown.

“There’s still a lot for us to learn,” Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said at the annual meeting of the American Academy of Dermatology. “Multiple factors contribute to the variability in the skin microbiota, including age, sex, environment, immune system, host genotype, lifestyle, and pathobiology. The question becomes, when do these factors or impacts on the microbiota become clinically significant?”

According to Dr. Friedman, there are 10 times more bacteria cells than human cells in the human body, “but it’s not a fight to the finish; it’s not us versus them,” he said. “Together, we are a super organism.” There are also more than 500 species of bacteria on human skin excluding viruses and fungi, and each person carries up to 5 pounds of bacteria, which is akin to finding a new organ in the body.

Credit: Daryl Leja, NHGRI (National Human Genome Research Institute)

“What’s so unique is that we each have our own bacterial fingerprint,” he said. “Whoever is sitting next to you? Their microbiota makeup is different than yours.”

Beyond genetics and environment, activities that can contribute to alterations in skin flora or skin dysbiosis include topical application of steroids, antibiotics, retinoids, harsh soaps, chemical and physical exfoliants, and resurfacing techniques. “With anything we apply or do to the skin, we are literally changing the home of many microorganisms, for good or bad,” he said.

In the realm of atopic dermatitis (AD), Staphylococcus aureus has been implicated as an offender in the pathophysiology of the disease. “It’s not about one single species of Staphylococcus, though,” said Dr. Friedman, who also is director of translational research at George Washington University. “We’re finding out that, depending on the severity of disease, Staph. epidermis may be part of the problem as opposed to it just being about Staph. aureus. Furthermore, and more importantly, these changes in the microbiota, specifically a decrease in microbial diversity, has been shown to precede a disease flare, highlighting the central role of maintaining microbial diversity and by definition, supporting the living barrier in our management of AD.”

With this in mind, researchers in one study used high-throughput sequencing to evaluate the microbial communities associated with affected and unaffected skin of 49 patients with AD before and after emollient treatment. Following 84 days of emollient application, clinical symptoms of AD improved in 72% of the study population and Stenotrophomonas species were significantly more abundant among responders.