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Fewer preterm deliveries, and perinatal mortality down
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
FROM JAMA PEDIATRICS
Key clinical point: Preterm births and perinatal mortality decreased from 2007 to 2015.
Major finding: The proportion of births at 39-40 weeks increased from 54.5% to 60.2% between 2007 and 2015.
Study details: A retrospective cohort study of nearly 35 million singleton births.
Disclosures: The researchers reported that they had no conflicts of interest.
Source: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
Intravenous antiemetic combination is well tolerated
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
FROM ANNALS OF ONCOLOGY
Key clinical point: Intravenous fosnetupitant and palonosetron are as well tolerated as is oral formulation.
Major finding: Treatment-emergent adverse events were similar for intravenous and oral fosnetupitant and palonosetron combination.
Study details: Double-blind, randomized phase 3 study of 404 patients undergoing chemotherapy.
Disclosures: Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
Source: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
Marijuana: Most oncologists are having the conversation
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The majority of medical oncologists discuss medical marijuana use with their patients, though few feel knowledgeable on the subject.
Major finding: Nearly 80% of medical oncologists have discussed medical marijuana use with their patients, but only 29.4% of those surveyed felt sufficiently knowledgeable.
Study details: Survey of 237 medical oncologists.
Disclosures: No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
Source: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
Topical corticosteroid-retinoid combination effective in moderate to severe psoriasis
The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.
In the two studies, investigators randomized a total of 418 or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.
At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).
Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.
Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.
Most patients maintained these improvements over the 4-week posttreatment period.
Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.
The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.
SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.
The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.
In the two studies, investigators randomized a total of 418 or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.
At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).
Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.
Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.
Most patients maintained these improvements over the 4-week posttreatment period.
Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.
The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.
SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.
The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.
In the two studies, investigators randomized a total of 418 or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.
At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).
Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.
Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.
Most patients maintained these improvements over the 4-week posttreatment period.
Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.
The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.
SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.
FROM JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point: Topical halobetasol propionate and tazarotene can significantly improve plaque psoriasis symptoms.
Major finding: Nearly half of adults treated with topical halobetasol propionate and tazarotene were “clear” or “almost clear” after 8 weeks.
Study details: Two multicenter, double-blind, vehicle-controlled phase 3 studies of 418 adults with psoriasis.
Disclosures: The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including Valeant Pharmaceuticals. Five authors are employees of the company.
Source: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.
Obesity and weight loss both linked to RA disability
Both obesity and weight loss are associated with worsening disability from rheumatoid arthritis, new research suggests.
An analysis of data from two long-term clinical registries involving a total of 25,020 patients with rheumatoid arthritis and 62,484 person-years of follow-up revealed that severely obese individuals with RA had significantly higher Health Assessment Questionnaire or Multi-Dimensional-HAQ scores at enrollment, compared with overweight participants, even after adjusting for confounders such as age, sex, race, smoking, disease duration, and comorbidity.
At the same time however, researchers saw a significantly larger increase in Health Assessment Questionnaire scores per year in individuals who had lost 5% or more of their weight since the age of 30. This association was evident after adjusting for body mass index at enrollment but was significantly more pronounced in individuals who were underweight. There was also a dose-dependent relationship between weight loss and subsequent worsening of disability.
Joshua F. Baker, MD, of the Philadelphia VA Medical Center and the University of Pennsylvania, and his coauthors wrote that while cross-sectional studies have shown greater disability among obese patients with RA, the longitudinal effects of obesity hadn’t been well characterized.
“Greater risks of worsening of disability in severely obese patients with RA are hypothesized to reflect the direct impact of adiposity and related comorbidities as opposed to more aggressive disease and higher disease activity,” the authors wrote. “Furthermore, in this study, adjustment for CRP [C-reactive protein] and swollen joint counts over time did not attenuate associations between severe obesity and worsening disability in the VARA [Veterans Affairs RA] registry, suggesting associations are not easily explained by more severe inflammatory disease among obese individuals.”
Commenting on the association between weight loss and worsening of disability, the authors said this may be a function of patients with more severe chronic illness experiencing weight loss.
“In RA, active inflammatory joint disease, chronic illness, comorbid disease, and worsening overall health can all contribute to weight loss,” the authors said, pointing out that while the reasons for the weight loss in the study were unknown, weight loss seen in similar observational studies was more commonly unintentional than intentional.
“Therefore, while intentional weight loss might be expected to have direct beneficial effects with regard to physical functioning and disability, these benefits are likely to be outweighed by the more common scenario of unintentional weight loss in association with greater severity of chronic illness,” they wrote. Indeed, one of the two registries used in the study had previously found a strong correlation between weight loss and early risk of death.
They argued that this therefore still supported – rather than refuted – the accepted view that intentional weight loss was an important way to limit disability in people with rheumatoid arthritis.
One limitation of the study was the use of BMI to measure adiposity, which the authors suggested may not have been an accurate surrogate in people with chronic disease. They also acknowledged that measures of disease activity may be different between obese and nonobese patients, and adjusting for this was challenging.
Three authors acknowledged receiving grand awards from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.
SOURCE: Baker J et al. Arthritis Care Res. 2018 Apr 30. doi: 10.1002/acr.23579.
Both obesity and weight loss are associated with worsening disability from rheumatoid arthritis, new research suggests.
An analysis of data from two long-term clinical registries involving a total of 25,020 patients with rheumatoid arthritis and 62,484 person-years of follow-up revealed that severely obese individuals with RA had significantly higher Health Assessment Questionnaire or Multi-Dimensional-HAQ scores at enrollment, compared with overweight participants, even after adjusting for confounders such as age, sex, race, smoking, disease duration, and comorbidity.
At the same time however, researchers saw a significantly larger increase in Health Assessment Questionnaire scores per year in individuals who had lost 5% or more of their weight since the age of 30. This association was evident after adjusting for body mass index at enrollment but was significantly more pronounced in individuals who were underweight. There was also a dose-dependent relationship between weight loss and subsequent worsening of disability.
Joshua F. Baker, MD, of the Philadelphia VA Medical Center and the University of Pennsylvania, and his coauthors wrote that while cross-sectional studies have shown greater disability among obese patients with RA, the longitudinal effects of obesity hadn’t been well characterized.
“Greater risks of worsening of disability in severely obese patients with RA are hypothesized to reflect the direct impact of adiposity and related comorbidities as opposed to more aggressive disease and higher disease activity,” the authors wrote. “Furthermore, in this study, adjustment for CRP [C-reactive protein] and swollen joint counts over time did not attenuate associations between severe obesity and worsening disability in the VARA [Veterans Affairs RA] registry, suggesting associations are not easily explained by more severe inflammatory disease among obese individuals.”
Commenting on the association between weight loss and worsening of disability, the authors said this may be a function of patients with more severe chronic illness experiencing weight loss.
“In RA, active inflammatory joint disease, chronic illness, comorbid disease, and worsening overall health can all contribute to weight loss,” the authors said, pointing out that while the reasons for the weight loss in the study were unknown, weight loss seen in similar observational studies was more commonly unintentional than intentional.
“Therefore, while intentional weight loss might be expected to have direct beneficial effects with regard to physical functioning and disability, these benefits are likely to be outweighed by the more common scenario of unintentional weight loss in association with greater severity of chronic illness,” they wrote. Indeed, one of the two registries used in the study had previously found a strong correlation between weight loss and early risk of death.
They argued that this therefore still supported – rather than refuted – the accepted view that intentional weight loss was an important way to limit disability in people with rheumatoid arthritis.
One limitation of the study was the use of BMI to measure adiposity, which the authors suggested may not have been an accurate surrogate in people with chronic disease. They also acknowledged that measures of disease activity may be different between obese and nonobese patients, and adjusting for this was challenging.
Three authors acknowledged receiving grand awards from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.
SOURCE: Baker J et al. Arthritis Care Res. 2018 Apr 30. doi: 10.1002/acr.23579.
Both obesity and weight loss are associated with worsening disability from rheumatoid arthritis, new research suggests.
An analysis of data from two long-term clinical registries involving a total of 25,020 patients with rheumatoid arthritis and 62,484 person-years of follow-up revealed that severely obese individuals with RA had significantly higher Health Assessment Questionnaire or Multi-Dimensional-HAQ scores at enrollment, compared with overweight participants, even after adjusting for confounders such as age, sex, race, smoking, disease duration, and comorbidity.
At the same time however, researchers saw a significantly larger increase in Health Assessment Questionnaire scores per year in individuals who had lost 5% or more of their weight since the age of 30. This association was evident after adjusting for body mass index at enrollment but was significantly more pronounced in individuals who were underweight. There was also a dose-dependent relationship between weight loss and subsequent worsening of disability.
Joshua F. Baker, MD, of the Philadelphia VA Medical Center and the University of Pennsylvania, and his coauthors wrote that while cross-sectional studies have shown greater disability among obese patients with RA, the longitudinal effects of obesity hadn’t been well characterized.
“Greater risks of worsening of disability in severely obese patients with RA are hypothesized to reflect the direct impact of adiposity and related comorbidities as opposed to more aggressive disease and higher disease activity,” the authors wrote. “Furthermore, in this study, adjustment for CRP [C-reactive protein] and swollen joint counts over time did not attenuate associations between severe obesity and worsening disability in the VARA [Veterans Affairs RA] registry, suggesting associations are not easily explained by more severe inflammatory disease among obese individuals.”
Commenting on the association between weight loss and worsening of disability, the authors said this may be a function of patients with more severe chronic illness experiencing weight loss.
“In RA, active inflammatory joint disease, chronic illness, comorbid disease, and worsening overall health can all contribute to weight loss,” the authors said, pointing out that while the reasons for the weight loss in the study were unknown, weight loss seen in similar observational studies was more commonly unintentional than intentional.
“Therefore, while intentional weight loss might be expected to have direct beneficial effects with regard to physical functioning and disability, these benefits are likely to be outweighed by the more common scenario of unintentional weight loss in association with greater severity of chronic illness,” they wrote. Indeed, one of the two registries used in the study had previously found a strong correlation between weight loss and early risk of death.
They argued that this therefore still supported – rather than refuted – the accepted view that intentional weight loss was an important way to limit disability in people with rheumatoid arthritis.
One limitation of the study was the use of BMI to measure adiposity, which the authors suggested may not have been an accurate surrogate in people with chronic disease. They also acknowledged that measures of disease activity may be different between obese and nonobese patients, and adjusting for this was challenging.
Three authors acknowledged receiving grand awards from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.
SOURCE: Baker J et al. Arthritis Care Res. 2018 Apr 30. doi: 10.1002/acr.23579.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Major finding: Individuals who have lost 5% of their body weight since age 30 show significantly increased rheumatoid arthritis disability.
Study details: Analysis of long-term registry data for 25,020 patients with rheumatoid arthritis.
Disclosures: Three authors acknowledged receiving grand awards from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.
Source: Baker J et al. Arthritis Care Res. 2018 Apr 30. doi: 10.1002/acr.23579.
No benefits from bath emollients for childhood eczema
In a trial of 482 children with atopic dermatitis who were randomized to either use of prescribed emollient bath additives regularly for 12 months or no additives, in addition to usual care, there was no significant difference between the two groups in the patient-oriented eczema measure (POEM) – a score of symptoms in the previous week – for the first 16 weeks of treatment, reported Miriam Santer, MD, of the University of Southampton, England, and her coauthors. The mean POEM score was 7.5 in the bath additives group and 8.4 in the no bath additives group.
There also was no significant effect of emollient bath additives on the secondary outcomes, which included POEM over 52 weeks, dermatitis family impact, generic quality of life, number of eczema exacerbations, or topical corticosteroid or topical calcineurin inhibitor use.
The authors noted that there was the suggestion of benefit in children who bathed five or more times a week, and in children aged under 5 years, but in both cases, the numbers were small.
“Although there is evidence for the need for leave-on emollients and widespread clinical consensus around soap substitutes, there is less agreement about the potential additional benefits of bath additives and a dearth of evidence on their effectiveness,” wrote Dr. Santer and her associates. “Bath additives are, however, widely prescribed at a cost of more than 23 million pounds ($33 million US; 26 million euros) annually to the National Health Service in England.”
The bath emollients used in the study included Aveeno bath oil, and Oilatum bath additive and Balneum bath oil – products available largely in the United Kingdom – along with others. Adherence was reasonable, with 93% of participants in the emollient group using bath additives more than half or all the time, and 92% of those in the no bath additives group using them less than half the time or never.
The authors stressed that there was strong evidence that supported regular use of leave-on emollients, and clinical consensus around the use of emollients as soap substitutes. “These findings are timely for clinicians and prescribing advisers, as prescribing guidelines vary widely in their advice on the use of bath additives, and pressure on budgets has led to formularies becoming increasingly restrictive.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Santer M et al. BMJ 2018 May 2. doi: 10.1136/bmj.k1332
The National Institute for Health and Care Excellence in the United Kingdom currently recommends regular use of “emollient wash products” for children with eczema, despite the fact that little good evidence of their benefit exists. It is therefore heartening that this study has largely addressed that evidence gap: There was no statistically significant difference between those children prescribed one of three bath additives in addition to standard care and those who received standard care alone.
However, there is still the question of whether younger children – particularly those who are bathed daily – might still benefit from bath emollients. Likewise, children who experience recurrent skin infections may derive some additional benefit from emollient bath additives with antiseptic properties.
Carsten Flohr, MD, is with the St. John’s Institute of Dermatology at Kings College London, and Amina Ahmed is a patient panel member at the Centre of Evidence-Based Dermatology in Nottingham, England. These comments are taken from an editorial accompanying the article by Santer et al. (BMJ. 2018 May 2. doi: 10.1136/bmj.k1791.) No conflicts of interest were declared.
The National Institute for Health and Care Excellence in the United Kingdom currently recommends regular use of “emollient wash products” for children with eczema, despite the fact that little good evidence of their benefit exists. It is therefore heartening that this study has largely addressed that evidence gap: There was no statistically significant difference between those children prescribed one of three bath additives in addition to standard care and those who received standard care alone.
However, there is still the question of whether younger children – particularly those who are bathed daily – might still benefit from bath emollients. Likewise, children who experience recurrent skin infections may derive some additional benefit from emollient bath additives with antiseptic properties.
Carsten Flohr, MD, is with the St. John’s Institute of Dermatology at Kings College London, and Amina Ahmed is a patient panel member at the Centre of Evidence-Based Dermatology in Nottingham, England. These comments are taken from an editorial accompanying the article by Santer et al. (BMJ. 2018 May 2. doi: 10.1136/bmj.k1791.) No conflicts of interest were declared.
The National Institute for Health and Care Excellence in the United Kingdom currently recommends regular use of “emollient wash products” for children with eczema, despite the fact that little good evidence of their benefit exists. It is therefore heartening that this study has largely addressed that evidence gap: There was no statistically significant difference between those children prescribed one of three bath additives in addition to standard care and those who received standard care alone.
However, there is still the question of whether younger children – particularly those who are bathed daily – might still benefit from bath emollients. Likewise, children who experience recurrent skin infections may derive some additional benefit from emollient bath additives with antiseptic properties.
Carsten Flohr, MD, is with the St. John’s Institute of Dermatology at Kings College London, and Amina Ahmed is a patient panel member at the Centre of Evidence-Based Dermatology in Nottingham, England. These comments are taken from an editorial accompanying the article by Santer et al. (BMJ. 2018 May 2. doi: 10.1136/bmj.k1791.) No conflicts of interest were declared.
In a trial of 482 children with atopic dermatitis who were randomized to either use of prescribed emollient bath additives regularly for 12 months or no additives, in addition to usual care, there was no significant difference between the two groups in the patient-oriented eczema measure (POEM) – a score of symptoms in the previous week – for the first 16 weeks of treatment, reported Miriam Santer, MD, of the University of Southampton, England, and her coauthors. The mean POEM score was 7.5 in the bath additives group and 8.4 in the no bath additives group.
There also was no significant effect of emollient bath additives on the secondary outcomes, which included POEM over 52 weeks, dermatitis family impact, generic quality of life, number of eczema exacerbations, or topical corticosteroid or topical calcineurin inhibitor use.
The authors noted that there was the suggestion of benefit in children who bathed five or more times a week, and in children aged under 5 years, but in both cases, the numbers were small.
“Although there is evidence for the need for leave-on emollients and widespread clinical consensus around soap substitutes, there is less agreement about the potential additional benefits of bath additives and a dearth of evidence on their effectiveness,” wrote Dr. Santer and her associates. “Bath additives are, however, widely prescribed at a cost of more than 23 million pounds ($33 million US; 26 million euros) annually to the National Health Service in England.”
The bath emollients used in the study included Aveeno bath oil, and Oilatum bath additive and Balneum bath oil – products available largely in the United Kingdom – along with others. Adherence was reasonable, with 93% of participants in the emollient group using bath additives more than half or all the time, and 92% of those in the no bath additives group using them less than half the time or never.
The authors stressed that there was strong evidence that supported regular use of leave-on emollients, and clinical consensus around the use of emollients as soap substitutes. “These findings are timely for clinicians and prescribing advisers, as prescribing guidelines vary widely in their advice on the use of bath additives, and pressure on budgets has led to formularies becoming increasingly restrictive.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Santer M et al. BMJ 2018 May 2. doi: 10.1136/bmj.k1332
In a trial of 482 children with atopic dermatitis who were randomized to either use of prescribed emollient bath additives regularly for 12 months or no additives, in addition to usual care, there was no significant difference between the two groups in the patient-oriented eczema measure (POEM) – a score of symptoms in the previous week – for the first 16 weeks of treatment, reported Miriam Santer, MD, of the University of Southampton, England, and her coauthors. The mean POEM score was 7.5 in the bath additives group and 8.4 in the no bath additives group.
There also was no significant effect of emollient bath additives on the secondary outcomes, which included POEM over 52 weeks, dermatitis family impact, generic quality of life, number of eczema exacerbations, or topical corticosteroid or topical calcineurin inhibitor use.
The authors noted that there was the suggestion of benefit in children who bathed five or more times a week, and in children aged under 5 years, but in both cases, the numbers were small.
“Although there is evidence for the need for leave-on emollients and widespread clinical consensus around soap substitutes, there is less agreement about the potential additional benefits of bath additives and a dearth of evidence on their effectiveness,” wrote Dr. Santer and her associates. “Bath additives are, however, widely prescribed at a cost of more than 23 million pounds ($33 million US; 26 million euros) annually to the National Health Service in England.”
The bath emollients used in the study included Aveeno bath oil, and Oilatum bath additive and Balneum bath oil – products available largely in the United Kingdom – along with others. Adherence was reasonable, with 93% of participants in the emollient group using bath additives more than half or all the time, and 92% of those in the no bath additives group using them less than half the time or never.
The authors stressed that there was strong evidence that supported regular use of leave-on emollients, and clinical consensus around the use of emollients as soap substitutes. “These findings are timely for clinicians and prescribing advisers, as prescribing guidelines vary widely in their advice on the use of bath additives, and pressure on budgets has led to formularies becoming increasingly restrictive.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Santer M et al. BMJ 2018 May 2. doi: 10.1136/bmj.k1332
FROM THE BMJ
Key clinical point: Emollient bath additives do not improve eczema scores in children.
Major finding: There was no significant difference in eczema scores between bath emollients or no bath emollients: the mean POEM score was 7.5 in the bath additives group and 8.4 in the no bath additives group.
Study details: An open-label randomized trial in 482 children with atopic dermatitis.
Disclosures: The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
Source: Santer M et al. BMJ 2018 May 2. doi: 10.1136/bmj.k1332
Early endovenous ablation speeds venous ulcer healing
Intervening early with endovenous ablation in patients with venous leg ulcers could significantly improve ulcer healing times and delay their recurrence, new research has found.
A randomized study presented at the International Charing Cross Symposium and published simultaneously in the April 24 issue of the New England Journal of Medicine compared the effects of early endovenous ablation with those of deferred ablation in 450 patients with venous leg ulcers, all of whom also received compression therapy.
The study showed that patients who received endovenous ablation within 2 weeks of randomization had significantly shorter healing times, compared with patients whose ablation was deferred for 6 months or until after the ulcer healed.
In the early-treatment group, the median time to ulcer healing was 56 days, while in the deferred-treatment group, it was 82 days. By 12 months, 93.8% of the early-intervention group had healed ulcers, compared with 85.8% in the deferred-intervention group.
Even after adjustment for factors such as patient age, ulcer size, ulcer duration, and recruitment center, patients who received early endovenous ablation were 38% more likely to have healed by 12 months, compared with the deferred-intervention group.
Researchers also saw significantly higher healing rates at 12 weeks in the early-intervention group, compared with the deferred-intervention group (63.5% vs. 51.6%, respectively).
“Observational studies have suggested that endovenous treatment of varicose veins – a treatment that may be particularly appropriate for the elderly population with venous leg ulcers – may improve ulcer healing,” wrote Manjit S. Gohel, MD, from the Cambridge (United Kingdom) University Hospitals NHS Foundation Trust and from Imperial College London and his coauthors. “In the current trial, we found that faster ulcer healing can be attained if an endovenous intervention is performed promptly.”
Early endovenous ablation also was associated with a delay in the recurrence of ulcers. The rate of recurrence was 11.4% among patients in the early-intervention group whose ulcers had healed and 16.5% among those in the delayed-intervention group whose ulcers had healed.
Patients who received the early endovenous ablation had a median ulcer-free time of 306 days, compared with 278 days in the delayed-intervention group, a significant difference.
The authors noted that all patients in the study also received high-quality compression therapy, which may account for the good healing rates seen in both groups that might not otherwise be observed in a real-world clinical setting.
“Accordingly, the improvement in ulcer healing with early endovenous intervention is likely to be greater in clinical practice than was observed in this trial,” the authors wrote. “Because endovenous intervention is usually performed as a single procedure, the clinical benefits are likely to be less dependent on ongoing patient adherence than they would be with compression therapy.”
The most common method for endovenous ablation used in this multicenter study was ultrasound-guided foam sclerotherapy, a minimally-invasive procedure the authors said had versatility and acceptability.
However, they commented that some previous, large randomized trials have suggested that the rates of complete venous occlusion are lower with foam sclerotherapy than with thermal ablation.
The main complications seen with endovenous ablation were pain and deep vein thrombosis.
The authors pointed out that two limitations of their trial were that patients with a leg ulcer that had been present for more than 6 months were excluded from patient selection and that the 450 patients enrolled had been selected from a larger group of around 6,500.
The study was supported by a grant from the National Institute for Health Research Health Technology Assessment Program. One author declared grants from a pharmaceutical company outside the submitted work, and seven declared funding from the NIHR as part of the conduct of the study. No other conflicts of interest were declared.
SOURCE: Gohel MS et al. NEJM. 2018 April 24. doi: 10.1056/NEJMoa1801214
Finally! A randomized controlled trial (RCT) which proves what we all kind of expected but which until now was unsupported by available literature. That is that endovenous ablation (EVA) in the presence of a concomitant venous ulcer not only decreases ulcer recurrence rates and increases ulcer-free time, it also significantly hastens ulcer healing times. I don’t know about you, but it always made sense to me that treatment of an incompetent saphenous vein, a known cause of ulceration, could be a factor in the time to ulcer healing.
But that’s what a whole host of retrospective and or nonrandomized studies seemed to suggest: Garbage in, garbage out. Enter the RCT – Issue resolved? Yes, with some caveats, and maybe no.
First, as the authors readily admit, the compression therapy which was applied to patients in both arms of the study was of “high quality” and would not likely be reproduced in real world practice. The authors also suggest that, in a real-world, clinical practice, the benefits of early EVA may prove to be even more pronounced because of poor patient compliance with compression. Not sure about that. In fact, if – in a real-world setting – the rate of compliance with compression in both groups turned out to be less than optimal, particularly in the patients who had EVA, the benefits of early ablation with respect to ulcer healing times might disappear.
In other words, we do not know from this study whether there would be the same advantages to early saphenous vein intervention without the addition of compression as compared with compression alone. This might explain why shorter ulcer healing times of EVA have been difficult to prove in non-RCT, more real-world studies. Perhaps a randomized trial comparing ulcer healing times with early EVA without compression versus compression therapy only? Hmmm.
Also, would the outcomes of the current study be similar on this side of the pond? Only 31.7% of limbs were treated with endothermal ablation only, by far the most common form of ablation performed in the United States. Almost 65% of limbs in the study were ablated with either foamed sclerotherapy alone or in conjunction with endothermal or mechanical modalities – not a common form of treatment here in the colonies. Inexplicably, the authors do not indicate whether outcomes were in any way influenced by the type of ablation performed. I am going to assume for now that it did not.
In summary, this study does not answer all the questions related to the use of EVA for the treatment of venous ulcers, but it comes pretty close. My take away is that there is no downside (or none that I can think of) to the use of EVA early on in the treatment of venous ulcers but a whole lot of potential upside for the patient. Now I, and probably you, have proof that what we were already doing really does have some increased benefit. Finally!
Alan M Dietzek, MD, is the Linda and Stephen R. Cohen Chair in Vascular Surgery at Danbury (Conn.) Hospital and a clinical professor of surgery at the University of Vermont, Burlington. He is also an associate medical editor for Vascular Specialist.
Finally! A randomized controlled trial (RCT) which proves what we all kind of expected but which until now was unsupported by available literature. That is that endovenous ablation (EVA) in the presence of a concomitant venous ulcer not only decreases ulcer recurrence rates and increases ulcer-free time, it also significantly hastens ulcer healing times. I don’t know about you, but it always made sense to me that treatment of an incompetent saphenous vein, a known cause of ulceration, could be a factor in the time to ulcer healing.
But that’s what a whole host of retrospective and or nonrandomized studies seemed to suggest: Garbage in, garbage out. Enter the RCT – Issue resolved? Yes, with some caveats, and maybe no.
First, as the authors readily admit, the compression therapy which was applied to patients in both arms of the study was of “high quality” and would not likely be reproduced in real world practice. The authors also suggest that, in a real-world, clinical practice, the benefits of early EVA may prove to be even more pronounced because of poor patient compliance with compression. Not sure about that. In fact, if – in a real-world setting – the rate of compliance with compression in both groups turned out to be less than optimal, particularly in the patients who had EVA, the benefits of early ablation with respect to ulcer healing times might disappear.
In other words, we do not know from this study whether there would be the same advantages to early saphenous vein intervention without the addition of compression as compared with compression alone. This might explain why shorter ulcer healing times of EVA have been difficult to prove in non-RCT, more real-world studies. Perhaps a randomized trial comparing ulcer healing times with early EVA without compression versus compression therapy only? Hmmm.
Also, would the outcomes of the current study be similar on this side of the pond? Only 31.7% of limbs were treated with endothermal ablation only, by far the most common form of ablation performed in the United States. Almost 65% of limbs in the study were ablated with either foamed sclerotherapy alone or in conjunction with endothermal or mechanical modalities – not a common form of treatment here in the colonies. Inexplicably, the authors do not indicate whether outcomes were in any way influenced by the type of ablation performed. I am going to assume for now that it did not.
In summary, this study does not answer all the questions related to the use of EVA for the treatment of venous ulcers, but it comes pretty close. My take away is that there is no downside (or none that I can think of) to the use of EVA early on in the treatment of venous ulcers but a whole lot of potential upside for the patient. Now I, and probably you, have proof that what we were already doing really does have some increased benefit. Finally!
Alan M Dietzek, MD, is the Linda and Stephen R. Cohen Chair in Vascular Surgery at Danbury (Conn.) Hospital and a clinical professor of surgery at the University of Vermont, Burlington. He is also an associate medical editor for Vascular Specialist.
Finally! A randomized controlled trial (RCT) which proves what we all kind of expected but which until now was unsupported by available literature. That is that endovenous ablation (EVA) in the presence of a concomitant venous ulcer not only decreases ulcer recurrence rates and increases ulcer-free time, it also significantly hastens ulcer healing times. I don’t know about you, but it always made sense to me that treatment of an incompetent saphenous vein, a known cause of ulceration, could be a factor in the time to ulcer healing.
But that’s what a whole host of retrospective and or nonrandomized studies seemed to suggest: Garbage in, garbage out. Enter the RCT – Issue resolved? Yes, with some caveats, and maybe no.
First, as the authors readily admit, the compression therapy which was applied to patients in both arms of the study was of “high quality” and would not likely be reproduced in real world practice. The authors also suggest that, in a real-world, clinical practice, the benefits of early EVA may prove to be even more pronounced because of poor patient compliance with compression. Not sure about that. In fact, if – in a real-world setting – the rate of compliance with compression in both groups turned out to be less than optimal, particularly in the patients who had EVA, the benefits of early ablation with respect to ulcer healing times might disappear.
In other words, we do not know from this study whether there would be the same advantages to early saphenous vein intervention without the addition of compression as compared with compression alone. This might explain why shorter ulcer healing times of EVA have been difficult to prove in non-RCT, more real-world studies. Perhaps a randomized trial comparing ulcer healing times with early EVA without compression versus compression therapy only? Hmmm.
Also, would the outcomes of the current study be similar on this side of the pond? Only 31.7% of limbs were treated with endothermal ablation only, by far the most common form of ablation performed in the United States. Almost 65% of limbs in the study were ablated with either foamed sclerotherapy alone or in conjunction with endothermal or mechanical modalities – not a common form of treatment here in the colonies. Inexplicably, the authors do not indicate whether outcomes were in any way influenced by the type of ablation performed. I am going to assume for now that it did not.
In summary, this study does not answer all the questions related to the use of EVA for the treatment of venous ulcers, but it comes pretty close. My take away is that there is no downside (or none that I can think of) to the use of EVA early on in the treatment of venous ulcers but a whole lot of potential upside for the patient. Now I, and probably you, have proof that what we were already doing really does have some increased benefit. Finally!
Alan M Dietzek, MD, is the Linda and Stephen R. Cohen Chair in Vascular Surgery at Danbury (Conn.) Hospital and a clinical professor of surgery at the University of Vermont, Burlington. He is also an associate medical editor for Vascular Specialist.
Intervening early with endovenous ablation in patients with venous leg ulcers could significantly improve ulcer healing times and delay their recurrence, new research has found.
A randomized study presented at the International Charing Cross Symposium and published simultaneously in the April 24 issue of the New England Journal of Medicine compared the effects of early endovenous ablation with those of deferred ablation in 450 patients with venous leg ulcers, all of whom also received compression therapy.
The study showed that patients who received endovenous ablation within 2 weeks of randomization had significantly shorter healing times, compared with patients whose ablation was deferred for 6 months or until after the ulcer healed.
In the early-treatment group, the median time to ulcer healing was 56 days, while in the deferred-treatment group, it was 82 days. By 12 months, 93.8% of the early-intervention group had healed ulcers, compared with 85.8% in the deferred-intervention group.
Even after adjustment for factors such as patient age, ulcer size, ulcer duration, and recruitment center, patients who received early endovenous ablation were 38% more likely to have healed by 12 months, compared with the deferred-intervention group.
Researchers also saw significantly higher healing rates at 12 weeks in the early-intervention group, compared with the deferred-intervention group (63.5% vs. 51.6%, respectively).
“Observational studies have suggested that endovenous treatment of varicose veins – a treatment that may be particularly appropriate for the elderly population with venous leg ulcers – may improve ulcer healing,” wrote Manjit S. Gohel, MD, from the Cambridge (United Kingdom) University Hospitals NHS Foundation Trust and from Imperial College London and his coauthors. “In the current trial, we found that faster ulcer healing can be attained if an endovenous intervention is performed promptly.”
Early endovenous ablation also was associated with a delay in the recurrence of ulcers. The rate of recurrence was 11.4% among patients in the early-intervention group whose ulcers had healed and 16.5% among those in the delayed-intervention group whose ulcers had healed.
Patients who received the early endovenous ablation had a median ulcer-free time of 306 days, compared with 278 days in the delayed-intervention group, a significant difference.
The authors noted that all patients in the study also received high-quality compression therapy, which may account for the good healing rates seen in both groups that might not otherwise be observed in a real-world clinical setting.
“Accordingly, the improvement in ulcer healing with early endovenous intervention is likely to be greater in clinical practice than was observed in this trial,” the authors wrote. “Because endovenous intervention is usually performed as a single procedure, the clinical benefits are likely to be less dependent on ongoing patient adherence than they would be with compression therapy.”
The most common method for endovenous ablation used in this multicenter study was ultrasound-guided foam sclerotherapy, a minimally-invasive procedure the authors said had versatility and acceptability.
However, they commented that some previous, large randomized trials have suggested that the rates of complete venous occlusion are lower with foam sclerotherapy than with thermal ablation.
The main complications seen with endovenous ablation were pain and deep vein thrombosis.
The authors pointed out that two limitations of their trial were that patients with a leg ulcer that had been present for more than 6 months were excluded from patient selection and that the 450 patients enrolled had been selected from a larger group of around 6,500.
The study was supported by a grant from the National Institute for Health Research Health Technology Assessment Program. One author declared grants from a pharmaceutical company outside the submitted work, and seven declared funding from the NIHR as part of the conduct of the study. No other conflicts of interest were declared.
SOURCE: Gohel MS et al. NEJM. 2018 April 24. doi: 10.1056/NEJMoa1801214
Intervening early with endovenous ablation in patients with venous leg ulcers could significantly improve ulcer healing times and delay their recurrence, new research has found.
A randomized study presented at the International Charing Cross Symposium and published simultaneously in the April 24 issue of the New England Journal of Medicine compared the effects of early endovenous ablation with those of deferred ablation in 450 patients with venous leg ulcers, all of whom also received compression therapy.
The study showed that patients who received endovenous ablation within 2 weeks of randomization had significantly shorter healing times, compared with patients whose ablation was deferred for 6 months or until after the ulcer healed.
In the early-treatment group, the median time to ulcer healing was 56 days, while in the deferred-treatment group, it was 82 days. By 12 months, 93.8% of the early-intervention group had healed ulcers, compared with 85.8% in the deferred-intervention group.
Even after adjustment for factors such as patient age, ulcer size, ulcer duration, and recruitment center, patients who received early endovenous ablation were 38% more likely to have healed by 12 months, compared with the deferred-intervention group.
Researchers also saw significantly higher healing rates at 12 weeks in the early-intervention group, compared with the deferred-intervention group (63.5% vs. 51.6%, respectively).
“Observational studies have suggested that endovenous treatment of varicose veins – a treatment that may be particularly appropriate for the elderly population with venous leg ulcers – may improve ulcer healing,” wrote Manjit S. Gohel, MD, from the Cambridge (United Kingdom) University Hospitals NHS Foundation Trust and from Imperial College London and his coauthors. “In the current trial, we found that faster ulcer healing can be attained if an endovenous intervention is performed promptly.”
Early endovenous ablation also was associated with a delay in the recurrence of ulcers. The rate of recurrence was 11.4% among patients in the early-intervention group whose ulcers had healed and 16.5% among those in the delayed-intervention group whose ulcers had healed.
Patients who received the early endovenous ablation had a median ulcer-free time of 306 days, compared with 278 days in the delayed-intervention group, a significant difference.
The authors noted that all patients in the study also received high-quality compression therapy, which may account for the good healing rates seen in both groups that might not otherwise be observed in a real-world clinical setting.
“Accordingly, the improvement in ulcer healing with early endovenous intervention is likely to be greater in clinical practice than was observed in this trial,” the authors wrote. “Because endovenous intervention is usually performed as a single procedure, the clinical benefits are likely to be less dependent on ongoing patient adherence than they would be with compression therapy.”
The most common method for endovenous ablation used in this multicenter study was ultrasound-guided foam sclerotherapy, a minimally-invasive procedure the authors said had versatility and acceptability.
However, they commented that some previous, large randomized trials have suggested that the rates of complete venous occlusion are lower with foam sclerotherapy than with thermal ablation.
The main complications seen with endovenous ablation were pain and deep vein thrombosis.
The authors pointed out that two limitations of their trial were that patients with a leg ulcer that had been present for more than 6 months were excluded from patient selection and that the 450 patients enrolled had been selected from a larger group of around 6,500.
The study was supported by a grant from the National Institute for Health Research Health Technology Assessment Program. One author declared grants from a pharmaceutical company outside the submitted work, and seven declared funding from the NIHR as part of the conduct of the study. No other conflicts of interest were declared.
SOURCE: Gohel MS et al. NEJM. 2018 April 24. doi: 10.1056/NEJMoa1801214
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Early endovenous ablation can speed healing of venous ulcers.
Major finding: Median ulcer healing time was 56 days with early venous ablation, compared with 82 days with deferred ablation.
Study details: Randomized controlled trial in 450 patients with venous leg ulcers.
Disclosures: The study was supported by a grant from the National Institute for Health Research Health Technology Assessment Program. One author declared grants from a pharmaceutical company outside the submitted work, and seven declared funding from the NIHR as part of the conduct of the study. No other conflicts of interest were declared.
Source: Gohel M et al. NEJM. 2018 April 24. doi: 10.1056/NEJMoa1801214
World Trade Center responders face greater cancer burden, including greater risk of multiple myeloma
Rescue and recovery workers who were involved in the aftermath of the World Trade Center disaster may face a greater cancer burden than the general population, according to two studies published in JAMA Oncology.
In particular, they may be at risk of developing multiple myeloma at an earlier age.
The first study was a closed-cohort study of 14,474 employees of the Fire Department of the City of New York (FDNY) who were exposed to the World Trade Center disaster but were cancer-free as of Jan. 1, 2012. The aim was to project cancer incidence from 2012 through 2031, based on data from the FDNY World Trade Center Health Program, and compare those rates with age-, race-, and sex-specific New York cancer rates from the general population.
The modeling projected a “modestly” higher number of cancer cases in the white male subgroup of rescue and recovery workers exposed to the World Trade Center (2,714 vs. 2,596 for the general population of New York; P less than .001). Specifically, the investigators projected significantly higher case counts of prostate cancer (1,437 vs. 863), thyroid cancer (73 vs. 57), and melanoma (201 vs. 131), compared with the general population in New York, but fewer lung (237 vs. 373), colorectal (172 vs. 267), and kidney cancers (66 vs. 132) (P less than .001 for all).
“Our findings suggest that the FDNY WTC-exposed cohort may experience a greater burden of cancer than would be expected from a population with similar demographic characteristics,” wrote Rachel Zeig-Owens, DrPH, from the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, and coauthors, highlighting prostate cancer as a particular concern.
However, they also acknowledged that the elevated rates observed in people exposed to the World Trade Center disaster could be a result of increased surveillance, even though they did attempt to correct for that, and that firefighters in general might face higher risks.
“It is possible that firefighters have a higher risk of cancer than the general population owing to exposures associated with the occupation,” they wrote. However occupation could also have the opposite effect, as rescue and recovery workers tend to have lower smoking rates, which may explain the relatively low rates of certain cancers such as lung cancer, they said.
A second study examined the effect of the World Trade Center disaster on the risk of multiple myeloma and monoclonal gammopathies in exposed firefighters.
The seroprevalence study of monoclonal gammopathies of undetermined significance (MGUS) in 781 exposed firefighters revealed that the age-standardized prevalence of these was 76% higher in this population than it was in a white male reference population living in Minnesota.
In particular, the age-standardized prevalence of light-chain MGUS was more than threefold higher in exposed firefighters, compared with the reference population.
Researchers also analyzed a case series of 16 exposed white male firefighters who received a diagnosis of multiple myeloma after Sept. 11, 2001. Of the 14 patients for whom data on the monoclonal protein isotype was available, half had light-chain multiple myeloma.
“These findings are of interest due to previously observed associations between light-chain multiple myeloma and light-chain MGUS and exposure to toxins, and chronic immune stimulation,” wrote Ola Landgren, MD, PhD, from the Memorial Sloan Kettering Cancer Center and his coauthors.
Seven patients were also assessed for CD20 expression – a marker of poorer prognosis – and 71% were found to be CD20-positive, a prevalence around 3.5-fold higher than that seen in the general population.
The cohort with multiple myeloma was diagnosed on average 12 years younger than those in the general population. The authors commented that this was unlikely to be caused by lead-time bias because the time from first symptoms to clinical manifestation of the disease is usually around 1 year.
“Taken together, our results show that environmental exposure due to the WTC attacks is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype,” the authors wrote.
The first study was supported by the National Institute of Occupational Safety and Health; no conflicts of interest were declared.
The second study was supported by the V Foundation for Cancer Research, the Byrne Fund for the benefit of Memorial Sloan-Kettering Cancer Center, the National Cancer Institute, the Albert Einstein Cancer Center, and the National Institute for Occupational Safety and Health; no conflicts of interest were declared.
SOURCE: Zeig-Owens R et al. JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0504. Landgren O et al. JAMA Oncology. 2018 April 16. doi: 10.1001/jamaoncol.2018.0509.
When the heroes of the World Trade Center are diagnosed with even a common cancer, there is a natural tendency to assume that the diagnosis is the result of their service during the disaster. However, it is important to appreciate that the firefighting profession is known to be associated with higher risks of monoclonal gammopathy of undetermined significance and multiple myelomas, compared with the general population.
Given that, it would have been preferable to compare the World Trade Center–exposed populations with an equally intensively screened, age-matched cohort of firefighters from another major city.
If we apply Sir Richard Doll’s rule that a single epidemiologic study cannot be persuasive until the lower bound of the 95% confidence interval is greater than three, the relative risks in the study by Landgren and colleagues are too small to be persuasive.
The predicted increases in cancers of the prostate, thyroid, and myeloma are interesting, but these have also been previously reported in firefighters from other cities.
Despite this, we owe it to these men and women to find the truth and determine the illnesses that are associated with their service.
Otis W. Brawley, MD, is chief medical and scientific officer and executive vice president of the American Cancer Society and a professor at Emory University, Atlanta. These comments are taken from an accompanying editorial (JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0498.) No conflicts of interest were declared.
When the heroes of the World Trade Center are diagnosed with even a common cancer, there is a natural tendency to assume that the diagnosis is the result of their service during the disaster. However, it is important to appreciate that the firefighting profession is known to be associated with higher risks of monoclonal gammopathy of undetermined significance and multiple myelomas, compared with the general population.
Given that, it would have been preferable to compare the World Trade Center–exposed populations with an equally intensively screened, age-matched cohort of firefighters from another major city.
If we apply Sir Richard Doll’s rule that a single epidemiologic study cannot be persuasive until the lower bound of the 95% confidence interval is greater than three, the relative risks in the study by Landgren and colleagues are too small to be persuasive.
The predicted increases in cancers of the prostate, thyroid, and myeloma are interesting, but these have also been previously reported in firefighters from other cities.
Despite this, we owe it to these men and women to find the truth and determine the illnesses that are associated with their service.
Otis W. Brawley, MD, is chief medical and scientific officer and executive vice president of the American Cancer Society and a professor at Emory University, Atlanta. These comments are taken from an accompanying editorial (JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0498.) No conflicts of interest were declared.
When the heroes of the World Trade Center are diagnosed with even a common cancer, there is a natural tendency to assume that the diagnosis is the result of their service during the disaster. However, it is important to appreciate that the firefighting profession is known to be associated with higher risks of monoclonal gammopathy of undetermined significance and multiple myelomas, compared with the general population.
Given that, it would have been preferable to compare the World Trade Center–exposed populations with an equally intensively screened, age-matched cohort of firefighters from another major city.
If we apply Sir Richard Doll’s rule that a single epidemiologic study cannot be persuasive until the lower bound of the 95% confidence interval is greater than three, the relative risks in the study by Landgren and colleagues are too small to be persuasive.
The predicted increases in cancers of the prostate, thyroid, and myeloma are interesting, but these have also been previously reported in firefighters from other cities.
Despite this, we owe it to these men and women to find the truth and determine the illnesses that are associated with their service.
Otis W. Brawley, MD, is chief medical and scientific officer and executive vice president of the American Cancer Society and a professor at Emory University, Atlanta. These comments are taken from an accompanying editorial (JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0498.) No conflicts of interest were declared.
Rescue and recovery workers who were involved in the aftermath of the World Trade Center disaster may face a greater cancer burden than the general population, according to two studies published in JAMA Oncology.
In particular, they may be at risk of developing multiple myeloma at an earlier age.
The first study was a closed-cohort study of 14,474 employees of the Fire Department of the City of New York (FDNY) who were exposed to the World Trade Center disaster but were cancer-free as of Jan. 1, 2012. The aim was to project cancer incidence from 2012 through 2031, based on data from the FDNY World Trade Center Health Program, and compare those rates with age-, race-, and sex-specific New York cancer rates from the general population.
The modeling projected a “modestly” higher number of cancer cases in the white male subgroup of rescue and recovery workers exposed to the World Trade Center (2,714 vs. 2,596 for the general population of New York; P less than .001). Specifically, the investigators projected significantly higher case counts of prostate cancer (1,437 vs. 863), thyroid cancer (73 vs. 57), and melanoma (201 vs. 131), compared with the general population in New York, but fewer lung (237 vs. 373), colorectal (172 vs. 267), and kidney cancers (66 vs. 132) (P less than .001 for all).
“Our findings suggest that the FDNY WTC-exposed cohort may experience a greater burden of cancer than would be expected from a population with similar demographic characteristics,” wrote Rachel Zeig-Owens, DrPH, from the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, and coauthors, highlighting prostate cancer as a particular concern.
However, they also acknowledged that the elevated rates observed in people exposed to the World Trade Center disaster could be a result of increased surveillance, even though they did attempt to correct for that, and that firefighters in general might face higher risks.
“It is possible that firefighters have a higher risk of cancer than the general population owing to exposures associated with the occupation,” they wrote. However occupation could also have the opposite effect, as rescue and recovery workers tend to have lower smoking rates, which may explain the relatively low rates of certain cancers such as lung cancer, they said.
A second study examined the effect of the World Trade Center disaster on the risk of multiple myeloma and monoclonal gammopathies in exposed firefighters.
The seroprevalence study of monoclonal gammopathies of undetermined significance (MGUS) in 781 exposed firefighters revealed that the age-standardized prevalence of these was 76% higher in this population than it was in a white male reference population living in Minnesota.
In particular, the age-standardized prevalence of light-chain MGUS was more than threefold higher in exposed firefighters, compared with the reference population.
Researchers also analyzed a case series of 16 exposed white male firefighters who received a diagnosis of multiple myeloma after Sept. 11, 2001. Of the 14 patients for whom data on the monoclonal protein isotype was available, half had light-chain multiple myeloma.
“These findings are of interest due to previously observed associations between light-chain multiple myeloma and light-chain MGUS and exposure to toxins, and chronic immune stimulation,” wrote Ola Landgren, MD, PhD, from the Memorial Sloan Kettering Cancer Center and his coauthors.
Seven patients were also assessed for CD20 expression – a marker of poorer prognosis – and 71% were found to be CD20-positive, a prevalence around 3.5-fold higher than that seen in the general population.
The cohort with multiple myeloma was diagnosed on average 12 years younger than those in the general population. The authors commented that this was unlikely to be caused by lead-time bias because the time from first symptoms to clinical manifestation of the disease is usually around 1 year.
“Taken together, our results show that environmental exposure due to the WTC attacks is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype,” the authors wrote.
The first study was supported by the National Institute of Occupational Safety and Health; no conflicts of interest were declared.
The second study was supported by the V Foundation for Cancer Research, the Byrne Fund for the benefit of Memorial Sloan-Kettering Cancer Center, the National Cancer Institute, the Albert Einstein Cancer Center, and the National Institute for Occupational Safety and Health; no conflicts of interest were declared.
SOURCE: Zeig-Owens R et al. JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0504. Landgren O et al. JAMA Oncology. 2018 April 16. doi: 10.1001/jamaoncol.2018.0509.
Rescue and recovery workers who were involved in the aftermath of the World Trade Center disaster may face a greater cancer burden than the general population, according to two studies published in JAMA Oncology.
In particular, they may be at risk of developing multiple myeloma at an earlier age.
The first study was a closed-cohort study of 14,474 employees of the Fire Department of the City of New York (FDNY) who were exposed to the World Trade Center disaster but were cancer-free as of Jan. 1, 2012. The aim was to project cancer incidence from 2012 through 2031, based on data from the FDNY World Trade Center Health Program, and compare those rates with age-, race-, and sex-specific New York cancer rates from the general population.
The modeling projected a “modestly” higher number of cancer cases in the white male subgroup of rescue and recovery workers exposed to the World Trade Center (2,714 vs. 2,596 for the general population of New York; P less than .001). Specifically, the investigators projected significantly higher case counts of prostate cancer (1,437 vs. 863), thyroid cancer (73 vs. 57), and melanoma (201 vs. 131), compared with the general population in New York, but fewer lung (237 vs. 373), colorectal (172 vs. 267), and kidney cancers (66 vs. 132) (P less than .001 for all).
“Our findings suggest that the FDNY WTC-exposed cohort may experience a greater burden of cancer than would be expected from a population with similar demographic characteristics,” wrote Rachel Zeig-Owens, DrPH, from the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, and coauthors, highlighting prostate cancer as a particular concern.
However, they also acknowledged that the elevated rates observed in people exposed to the World Trade Center disaster could be a result of increased surveillance, even though they did attempt to correct for that, and that firefighters in general might face higher risks.
“It is possible that firefighters have a higher risk of cancer than the general population owing to exposures associated with the occupation,” they wrote. However occupation could also have the opposite effect, as rescue and recovery workers tend to have lower smoking rates, which may explain the relatively low rates of certain cancers such as lung cancer, they said.
A second study examined the effect of the World Trade Center disaster on the risk of multiple myeloma and monoclonal gammopathies in exposed firefighters.
The seroprevalence study of monoclonal gammopathies of undetermined significance (MGUS) in 781 exposed firefighters revealed that the age-standardized prevalence of these was 76% higher in this population than it was in a white male reference population living in Minnesota.
In particular, the age-standardized prevalence of light-chain MGUS was more than threefold higher in exposed firefighters, compared with the reference population.
Researchers also analyzed a case series of 16 exposed white male firefighters who received a diagnosis of multiple myeloma after Sept. 11, 2001. Of the 14 patients for whom data on the monoclonal protein isotype was available, half had light-chain multiple myeloma.
“These findings are of interest due to previously observed associations between light-chain multiple myeloma and light-chain MGUS and exposure to toxins, and chronic immune stimulation,” wrote Ola Landgren, MD, PhD, from the Memorial Sloan Kettering Cancer Center and his coauthors.
Seven patients were also assessed for CD20 expression – a marker of poorer prognosis – and 71% were found to be CD20-positive, a prevalence around 3.5-fold higher than that seen in the general population.
The cohort with multiple myeloma was diagnosed on average 12 years younger than those in the general population. The authors commented that this was unlikely to be caused by lead-time bias because the time from first symptoms to clinical manifestation of the disease is usually around 1 year.
“Taken together, our results show that environmental exposure due to the WTC attacks is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype,” the authors wrote.
The first study was supported by the National Institute of Occupational Safety and Health; no conflicts of interest were declared.
The second study was supported by the V Foundation for Cancer Research, the Byrne Fund for the benefit of Memorial Sloan-Kettering Cancer Center, the National Cancer Institute, the Albert Einstein Cancer Center, and the National Institute for Occupational Safety and Health; no conflicts of interest were declared.
SOURCE: Zeig-Owens R et al. JAMA Oncology. 2018 April 26. doi: 10.1001/jamaoncol.2018.0504. Landgren O et al. JAMA Oncology. 2018 April 16. doi: 10.1001/jamaoncol.2018.0509.
FROM JAMA ONCOLOGY
Key clinical point: Monoclonal gammopathies and multiple myeloma may occur more often and earlier in World Trade Center rescue workers.
Major finding: Prevalence of light-chain monoclonal gammopathies is threefold higher in exposed firefighters than in a reference population of white males.
Study details: A cohort study in 14,474 employees of the Fire Department of the City of New York exposed to the Sept. 11, 2001, World Trade Center disaster, a case series of 16 exposed white male firefighters diagnosed with multiple myeloma, and a seroprevalence study of monoclonal gammopathies of undetermined significance in 781 exposed firefighters.
Disclosures: The first study was supported by the National Institute of Occupational Safety and Health; no conflicts of interest were declared. The second study was supported by the V Foundation for Cancer Research, the Byrne Fund for the benefit of Memorial Sloan-Kettering Cancer Center, the National Cancer Institute, the Albert Einstein Cancer Center, and the National Institute for Occupational Safety and Health; no conflicts of interest were declared.
Source: Zeig-Owens R et al. JAMA Oncology 2018, Apr 26. doi: 10.1001/jamaoncol.2018.0504. Landgren O et al. JAMA Oncology 2018, Apr 26. doi: 10.1001/jamaoncol.2018.0509.
Substance use linked to conversion to schizophrenia
People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.
The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.
After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.
Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.
Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.
These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.
Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.
However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.
“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”
The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.
Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.
The Lundbeck Foundation supported the study. No conflicts of interest were declared.
SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.
People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.
The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.
After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.
Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.
Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.
These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.
Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.
However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.
“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”
The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.
Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.
The Lundbeck Foundation supported the study. No conflicts of interest were declared.
SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.
People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.
The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.
After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.
Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.
Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.
These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.
Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.
However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.
“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”
The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.
Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.
The Lundbeck Foundation supported the study. No conflicts of interest were declared.
SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.
FROM JAMA PSYCHIATRY
Key clinical point: Patients with schizotypal disorder who have substance use disorders are more likely to convert to schizophrenia.
Major finding: The conversion rate from schizotypal disorder to schizophrenia was 58.2% in individuals with substance use disorder.
Study details: Prospective cohort study in 2,539 individuals with schizotypal disorder.
Disclosures: The Lundbeck Foundation supported the study. No conflicts of interest were declared.
Source: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.
Triple-therapy cuts COPD exacerbations
Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.
The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).
The study randomized patients to 52 weeks of either triple inhaled therapy involving a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid), 62.5 mcg of the LAMA umeclidinium and 25 mcg of the LABA vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol.
After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).
When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.
Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.
“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.
Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.
Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.
Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.
All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.
The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.
At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.
“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.
Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.
“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”
The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.
SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.
The data from the IMPACT study fills a gap in the evidence supporting a step-up from dual to triple inhaled therapy for COPD, which so far has been recommended only for patients with severe loss of lung function and those with frequent exacerbations despite maximum bronchodilator treatment. The study has the strengths of comparing the step-up to triple therapy with the GOLD guideline–recommended dual therapies and using the same dosages in the triple therapy as in the dual therapy
However, it is important to note that nearly 40% of patients enrolled in the trial were already being treated with triple therapy, 70% were receiving a glucocorticoid, and patients with a history of asthma were not excluded. This means patients assigned to the dual therapy without glucocorticoids would have had an abrupt cessation of their glucocorticoid therapy, which may explain a rapid surge in exacerbations in the first month and the lower rate of exacerbations in the dual-therapy group that did include glucocorticoids. The choice of patients for the study could potentially have artificially inflated the observed effectiveness of triple therapy over dual bronchodilator treatment.
As such, we suggest clinicians stick with the GOLD 2017 recommendations that escalation to triple therapy only occur after maximization of bronchodilator treatment.
Dr. Samy Suissa (PhD) is with the Center for Clinical Epidemiology at Lady Davis Institute–Jewish General Hospital, and the departments of epidemiology and biostatistics and medicine at McGill University, Montreal. Dr. Jeffrey M. Drazen is editor-in-chief of the New England Journal of Medicine. These comments are taken from an editorial (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMe1716802 ). Dr. Suissa declared personal fees and grants from the pharmaceutical industry outside the submitted work.
The data from the IMPACT study fills a gap in the evidence supporting a step-up from dual to triple inhaled therapy for COPD, which so far has been recommended only for patients with severe loss of lung function and those with frequent exacerbations despite maximum bronchodilator treatment. The study has the strengths of comparing the step-up to triple therapy with the GOLD guideline–recommended dual therapies and using the same dosages in the triple therapy as in the dual therapy
However, it is important to note that nearly 40% of patients enrolled in the trial were already being treated with triple therapy, 70% were receiving a glucocorticoid, and patients with a history of asthma were not excluded. This means patients assigned to the dual therapy without glucocorticoids would have had an abrupt cessation of their glucocorticoid therapy, which may explain a rapid surge in exacerbations in the first month and the lower rate of exacerbations in the dual-therapy group that did include glucocorticoids. The choice of patients for the study could potentially have artificially inflated the observed effectiveness of triple therapy over dual bronchodilator treatment.
As such, we suggest clinicians stick with the GOLD 2017 recommendations that escalation to triple therapy only occur after maximization of bronchodilator treatment.
Dr. Samy Suissa (PhD) is with the Center for Clinical Epidemiology at Lady Davis Institute–Jewish General Hospital, and the departments of epidemiology and biostatistics and medicine at McGill University, Montreal. Dr. Jeffrey M. Drazen is editor-in-chief of the New England Journal of Medicine. These comments are taken from an editorial (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMe1716802 ). Dr. Suissa declared personal fees and grants from the pharmaceutical industry outside the submitted work.
The data from the IMPACT study fills a gap in the evidence supporting a step-up from dual to triple inhaled therapy for COPD, which so far has been recommended only for patients with severe loss of lung function and those with frequent exacerbations despite maximum bronchodilator treatment. The study has the strengths of comparing the step-up to triple therapy with the GOLD guideline–recommended dual therapies and using the same dosages in the triple therapy as in the dual therapy
However, it is important to note that nearly 40% of patients enrolled in the trial were already being treated with triple therapy, 70% were receiving a glucocorticoid, and patients with a history of asthma were not excluded. This means patients assigned to the dual therapy without glucocorticoids would have had an abrupt cessation of their glucocorticoid therapy, which may explain a rapid surge in exacerbations in the first month and the lower rate of exacerbations in the dual-therapy group that did include glucocorticoids. The choice of patients for the study could potentially have artificially inflated the observed effectiveness of triple therapy over dual bronchodilator treatment.
As such, we suggest clinicians stick with the GOLD 2017 recommendations that escalation to triple therapy only occur after maximization of bronchodilator treatment.
Dr. Samy Suissa (PhD) is with the Center for Clinical Epidemiology at Lady Davis Institute–Jewish General Hospital, and the departments of epidemiology and biostatistics and medicine at McGill University, Montreal. Dr. Jeffrey M. Drazen is editor-in-chief of the New England Journal of Medicine. These comments are taken from an editorial (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMe1716802 ). Dr. Suissa declared personal fees and grants from the pharmaceutical industry outside the submitted work.
Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.
The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).
The study randomized patients to 52 weeks of either triple inhaled therapy involving a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid), 62.5 mcg of the LAMA umeclidinium and 25 mcg of the LABA vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol.
After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).
When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.
Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.
“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.
Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.
Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.
Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.
All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.
The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.
At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.
“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.
Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.
“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”
The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.
SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.
Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.
The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).
The study randomized patients to 52 weeks of either triple inhaled therapy involving a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid), 62.5 mcg of the LAMA umeclidinium and 25 mcg of the LABA vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol.
After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).
When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.
Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.
“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.
Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.
Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.
Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.
All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.
The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.
At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.
“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.
Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.
“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”
The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.
SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Triple COPD therapy shows fewer exacerbations than does dual therapy.
Major finding: Triple COPD therapy achieves a 15%-25% greater reduction in exacerbations compared with dual therapy.
Study details: Randomized controlled trial of 10,355 patients with symptomatic COPD.
Disclosures: The study was funded by GlaxoSmithKline, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GlaxoSmithKline and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GlaxoSmithKline. One author had no conflicts of interest to declare.
Source: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.