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Genetic variants linked to HSCT outcomes in ALL
ORLANDO, FL—Results of a genome-wide association study suggest that several genetic variants are associated with outcomes of allogeneic hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia (ALL).
Investigators identified several single-nucleotide polymorphisms (SNPs) in ALL patients and their unrelated donors that were associated with disease-related death or progression-free survival (PFS) within 1 year of HSCT.
“We believe that these findings will lead to a better understanding of the biology of this disease,” said investigator Theresa Hahn, PhD, of Roswell Park Cancer Institute in Buffalo, New York.
“Additionally, we expect that this work will eventually help clinical teams to identify unrelated donors with genotypes that yield better survival in transplant patients and enhance the chances for successful blood and marrow transplants.”
Dr Hahn presented this work as a “Best Abstract” at the 2017 BMT Tandem Meetings (abstract 1).
For this study, she and her colleagues analyzed data on patients treated at more than 150 US transplant centers between 2000 and 2011. The investigators evaluated data on more than 3000 patients with acute leukemias or myelodysplastic syndromes, but Dr Hahn only presented findings in the ALL patients and their donors.
The patients and donors were divided into 2 cohorts. Cohort 1 included 483 ALL patients who underwent HSCT from 2000 to 2008 and 466 unrelated donors who were a 10/10 HLA match for the patients.
Cohort 2 included 94 ALL patients who received a transplant from a 10/10 HLA-matched donor between 2009 and 2011 or from an 8/8 HLA-matched donor between 2000 and 2011. There were 92 donors in this cohort.
The investigators sequenced blood samples from the recipients and donors to identify SNPs. The SNPs were then measured for association with disease-related death and PFS using Cox proportional hazards models adjusted for recipient age, disease status at HSCT (early, intermediate, or advanced), graft source (blood or marrow), and year of transplant.
SNPs in donors
The top 2 SNPs in donors that were associated with a significant increase in disease-related death were:
- rs79503405 in LRP2 on chromosome 2.
- rs77618918 in ASIC2 on chromosome 17.
Dr Hahn noted that rs79503405 is in complete linkage disequilibrium (r2=1.0) with a genotyped missense variant (rs17848149) and a synonymous coding variant (rs35114151) in LRP2.
She also pointed out that the other top SNP (rs77618918) associated with disease-related death is not in linkage disequilibrium with other SNPs of functional importance, so the significance of this SNP is unknown.
There were no SNPs in donors that were significantly associated with PFS.
SNPs in recipients
In HSCT recipients, there were 3 linked variants in NRG1 on chromosome 8 (rs79853417, rs6990973, and rs145488394) that were significantly associated with disease-related death.
Another SNP (rs60640657) on chromosome 2 (CTNNA3/LOC101928961/LRRTM3) was also significantly associated with ALL-related death.
In addition, Dr Hahn and her colleagues found that 1 region in recipient genomes contains multiple variants (rs113263921 and others) associated with PFS. The SNPs are located on chromosome 3 in MLH1 and TRANK1.
“The donor and recipient genetic variants contributed independently to death due to ALL,” Dr Hahn said in closing. “Genetic variants for PFS do not overlap with death due to ALL, and this is probably due to the inclusion of both non-fatal disease progression as well as transplant-related mortality in the definition of PFS.”
“Constitutional genetic variants in recipients and donors increase the risk of death due to ALL, and they warrant further study into the impact of these genes on disease and transplant-related biology.” 
ORLANDO, FL—Results of a genome-wide association study suggest that several genetic variants are associated with outcomes of allogeneic hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia (ALL).
Investigators identified several single-nucleotide polymorphisms (SNPs) in ALL patients and their unrelated donors that were associated with disease-related death or progression-free survival (PFS) within 1 year of HSCT.
“We believe that these findings will lead to a better understanding of the biology of this disease,” said investigator Theresa Hahn, PhD, of Roswell Park Cancer Institute in Buffalo, New York.
“Additionally, we expect that this work will eventually help clinical teams to identify unrelated donors with genotypes that yield better survival in transplant patients and enhance the chances for successful blood and marrow transplants.”
Dr Hahn presented this work as a “Best Abstract” at the 2017 BMT Tandem Meetings (abstract 1).
For this study, she and her colleagues analyzed data on patients treated at more than 150 US transplant centers between 2000 and 2011. The investigators evaluated data on more than 3000 patients with acute leukemias or myelodysplastic syndromes, but Dr Hahn only presented findings in the ALL patients and their donors.
The patients and donors were divided into 2 cohorts. Cohort 1 included 483 ALL patients who underwent HSCT from 2000 to 2008 and 466 unrelated donors who were a 10/10 HLA match for the patients.
Cohort 2 included 94 ALL patients who received a transplant from a 10/10 HLA-matched donor between 2009 and 2011 or from an 8/8 HLA-matched donor between 2000 and 2011. There were 92 donors in this cohort.
The investigators sequenced blood samples from the recipients and donors to identify SNPs. The SNPs were then measured for association with disease-related death and PFS using Cox proportional hazards models adjusted for recipient age, disease status at HSCT (early, intermediate, or advanced), graft source (blood or marrow), and year of transplant.
SNPs in donors
The top 2 SNPs in donors that were associated with a significant increase in disease-related death were:
- rs79503405 in LRP2 on chromosome 2.
- rs77618918 in ASIC2 on chromosome 17.
Dr Hahn noted that rs79503405 is in complete linkage disequilibrium (r2=1.0) with a genotyped missense variant (rs17848149) and a synonymous coding variant (rs35114151) in LRP2.
She also pointed out that the other top SNP (rs77618918) associated with disease-related death is not in linkage disequilibrium with other SNPs of functional importance, so the significance of this SNP is unknown.
There were no SNPs in donors that were significantly associated with PFS.
SNPs in recipients
In HSCT recipients, there were 3 linked variants in NRG1 on chromosome 8 (rs79853417, rs6990973, and rs145488394) that were significantly associated with disease-related death.
Another SNP (rs60640657) on chromosome 2 (CTNNA3/LOC101928961/LRRTM3) was also significantly associated with ALL-related death.
In addition, Dr Hahn and her colleagues found that 1 region in recipient genomes contains multiple variants (rs113263921 and others) associated with PFS. The SNPs are located on chromosome 3 in MLH1 and TRANK1.
“The donor and recipient genetic variants contributed independently to death due to ALL,” Dr Hahn said in closing. “Genetic variants for PFS do not overlap with death due to ALL, and this is probably due to the inclusion of both non-fatal disease progression as well as transplant-related mortality in the definition of PFS.”
“Constitutional genetic variants in recipients and donors increase the risk of death due to ALL, and they warrant further study into the impact of these genes on disease and transplant-related biology.”
ORLANDO, FL—Results of a genome-wide association study suggest that several genetic variants are associated with outcomes of allogeneic hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia (ALL).
Investigators identified several single-nucleotide polymorphisms (SNPs) in ALL patients and their unrelated donors that were associated with disease-related death or progression-free survival (PFS) within 1 year of HSCT.
“We believe that these findings will lead to a better understanding of the biology of this disease,” said investigator Theresa Hahn, PhD, of Roswell Park Cancer Institute in Buffalo, New York.
“Additionally, we expect that this work will eventually help clinical teams to identify unrelated donors with genotypes that yield better survival in transplant patients and enhance the chances for successful blood and marrow transplants.”
Dr Hahn presented this work as a “Best Abstract” at the 2017 BMT Tandem Meetings (abstract 1).
For this study, she and her colleagues analyzed data on patients treated at more than 150 US transplant centers between 2000 and 2011. The investigators evaluated data on more than 3000 patients with acute leukemias or myelodysplastic syndromes, but Dr Hahn only presented findings in the ALL patients and their donors.
The patients and donors were divided into 2 cohorts. Cohort 1 included 483 ALL patients who underwent HSCT from 2000 to 2008 and 466 unrelated donors who were a 10/10 HLA match for the patients.
Cohort 2 included 94 ALL patients who received a transplant from a 10/10 HLA-matched donor between 2009 and 2011 or from an 8/8 HLA-matched donor between 2000 and 2011. There were 92 donors in this cohort.
The investigators sequenced blood samples from the recipients and donors to identify SNPs. The SNPs were then measured for association with disease-related death and PFS using Cox proportional hazards models adjusted for recipient age, disease status at HSCT (early, intermediate, or advanced), graft source (blood or marrow), and year of transplant.
SNPs in donors
The top 2 SNPs in donors that were associated with a significant increase in disease-related death were:
- rs79503405 in LRP2 on chromosome 2.
- rs77618918 in ASIC2 on chromosome 17.
Dr Hahn noted that rs79503405 is in complete linkage disequilibrium (r2=1.0) with a genotyped missense variant (rs17848149) and a synonymous coding variant (rs35114151) in LRP2.
She also pointed out that the other top SNP (rs77618918) associated with disease-related death is not in linkage disequilibrium with other SNPs of functional importance, so the significance of this SNP is unknown.
There were no SNPs in donors that were significantly associated with PFS.
SNPs in recipients
In HSCT recipients, there were 3 linked variants in NRG1 on chromosome 8 (rs79853417, rs6990973, and rs145488394) that were significantly associated with disease-related death.
Another SNP (rs60640657) on chromosome 2 (CTNNA3/LOC101928961/LRRTM3) was also significantly associated with ALL-related death.
In addition, Dr Hahn and her colleagues found that 1 region in recipient genomes contains multiple variants (rs113263921 and others) associated with PFS. The SNPs are located on chromosome 3 in MLH1 and TRANK1.
“The donor and recipient genetic variants contributed independently to death due to ALL,” Dr Hahn said in closing. “Genetic variants for PFS do not overlap with death due to ALL, and this is probably due to the inclusion of both non-fatal disease progression as well as transplant-related mortality in the definition of PFS.”
“Constitutional genetic variants in recipients and donors increase the risk of death due to ALL, and they warrant further study into the impact of these genes on disease and transplant-related biology.”
Combo prolongs OS in relapsed/refractory MM
NEW DEHLI—A 2-drug combination previously shown to prolong progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM) can prolong overall survival (OS) as well, according to researchers.
Updated results of the phase 3 ENDEAVOR trial showed that patients who received treatment with carfilzomib and dexamethasone had a 7.6-month benefit in median OS when compared to patients who received bortezomib and dexamethasone.
Previous results from this trial showed a 9.3-month benefit in median PFS with carfilzomib and dexamethasone.
“Based on these data, we now know that [carfilzomib] not only significantly extended progression-free survival compared to [bortezomib] but also overall survival, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma,” said Meletios A. Dimopoulos, MD, of the University of Athens in Greece.
Dr Dimopoulos presented OS results from ENDEAVOR at the 16th International Myeloma Workshop. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.
ENDEAVOR included 929 MM patients who had received 1 to 3 prior treatment regimens. The patients were randomized to receive carfilzomib and low-dose dexamethasone (n=464) or bortezomib and low-dose dexamethasone (n=465) until disease progression.
Baseline characteristics were similar between the treatment arms.
Detailed patient and treatment characteristics, as well as response and PFS data, have been previously reported.
OS and safety
The median OS was 47.6 months in the carfilzomib arm and 40.0 months in the bortezomib arm. All-cause mortality was significantly lower with the carfilzomib combination than the bortezomib combination (hazard ratio [HR]=0.791, 1-sided P=0.0100).
Researchers said there was an OS benefit with the carfilzomib combination whether or not patients received prior treatment with bortezomib and regardless of patients’ age, ECOG performance status at baseline, cytogenetic risk group, or the number of previous therapies they received.
The HR was 0.75 (carfilzomib vs bortezomib) for patients with no prior bortezomib and 0.84 for patients who received prior bortezomib. The HR was 0.85 for patients younger than 65, 0.71 for those ages 65 to 74, and 0.84 for patients age 75 and older.
The HR was 0.81 for patients with an ECOG status of 0, 0.80 for those with a status of 1, and 0.50 for those with a status of 2. The HR was 0.83 for patients with high-risk cytogenetics and 0.85 for those with standard-risk cytogenetics.
The HR was 0.83 for patients with 1 prior line of therapy and 0.76 for those with 2 to 3 prior lines of therapy.
The researchers said safety results in this analysis were comparable with previously reported results. The incidence of grade 3 or higher adverse events was 81.4% in the carfilzomib arm and 71.1% in the bortezomib arm.
The most common adverse events of any grade (in the carfilzomib and bortezomib arms, respectively) were anemia (42.5% and 28.3%), diarrhea (36.3% and 40.6%), pyrexia (32.4% and 15.4%), dyspnea (32.2% and 13.6%), fatigue (32.2% and 30.7%), and hypertension (32.2% and 9.9%).
NEW DEHLI—A 2-drug combination previously shown to prolong progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM) can prolong overall survival (OS) as well, according to researchers.
Updated results of the phase 3 ENDEAVOR trial showed that patients who received treatment with carfilzomib and dexamethasone had a 7.6-month benefit in median OS when compared to patients who received bortezomib and dexamethasone.
Previous results from this trial showed a 9.3-month benefit in median PFS with carfilzomib and dexamethasone.
“Based on these data, we now know that [carfilzomib] not only significantly extended progression-free survival compared to [bortezomib] but also overall survival, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma,” said Meletios A. Dimopoulos, MD, of the University of Athens in Greece.
Dr Dimopoulos presented OS results from ENDEAVOR at the 16th International Myeloma Workshop. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.
ENDEAVOR included 929 MM patients who had received 1 to 3 prior treatment regimens. The patients were randomized to receive carfilzomib and low-dose dexamethasone (n=464) or bortezomib and low-dose dexamethasone (n=465) until disease progression.
Baseline characteristics were similar between the treatment arms.
Detailed patient and treatment characteristics, as well as response and PFS data, have been previously reported.
OS and safety
The median OS was 47.6 months in the carfilzomib arm and 40.0 months in the bortezomib arm. All-cause mortality was significantly lower with the carfilzomib combination than the bortezomib combination (hazard ratio [HR]=0.791, 1-sided P=0.0100).
Researchers said there was an OS benefit with the carfilzomib combination whether or not patients received prior treatment with bortezomib and regardless of patients’ age, ECOG performance status at baseline, cytogenetic risk group, or the number of previous therapies they received.
The HR was 0.75 (carfilzomib vs bortezomib) for patients with no prior bortezomib and 0.84 for patients who received prior bortezomib. The HR was 0.85 for patients younger than 65, 0.71 for those ages 65 to 74, and 0.84 for patients age 75 and older.
The HR was 0.81 for patients with an ECOG status of 0, 0.80 for those with a status of 1, and 0.50 for those with a status of 2. The HR was 0.83 for patients with high-risk cytogenetics and 0.85 for those with standard-risk cytogenetics.
The HR was 0.83 for patients with 1 prior line of therapy and 0.76 for those with 2 to 3 prior lines of therapy.
The researchers said safety results in this analysis were comparable with previously reported results. The incidence of grade 3 or higher adverse events was 81.4% in the carfilzomib arm and 71.1% in the bortezomib arm.
The most common adverse events of any grade (in the carfilzomib and bortezomib arms, respectively) were anemia (42.5% and 28.3%), diarrhea (36.3% and 40.6%), pyrexia (32.4% and 15.4%), dyspnea (32.2% and 13.6%), fatigue (32.2% and 30.7%), and hypertension (32.2% and 9.9%).
NEW DEHLI—A 2-drug combination previously shown to prolong progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM) can prolong overall survival (OS) as well, according to researchers.
Updated results of the phase 3 ENDEAVOR trial showed that patients who received treatment with carfilzomib and dexamethasone had a 7.6-month benefit in median OS when compared to patients who received bortezomib and dexamethasone.
Previous results from this trial showed a 9.3-month benefit in median PFS with carfilzomib and dexamethasone.
“Based on these data, we now know that [carfilzomib] not only significantly extended progression-free survival compared to [bortezomib] but also overall survival, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma,” said Meletios A. Dimopoulos, MD, of the University of Athens in Greece.
Dr Dimopoulos presented OS results from ENDEAVOR at the 16th International Myeloma Workshop. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.
ENDEAVOR included 929 MM patients who had received 1 to 3 prior treatment regimens. The patients were randomized to receive carfilzomib and low-dose dexamethasone (n=464) or bortezomib and low-dose dexamethasone (n=465) until disease progression.
Baseline characteristics were similar between the treatment arms.
Detailed patient and treatment characteristics, as well as response and PFS data, have been previously reported.
OS and safety
The median OS was 47.6 months in the carfilzomib arm and 40.0 months in the bortezomib arm. All-cause mortality was significantly lower with the carfilzomib combination than the bortezomib combination (hazard ratio [HR]=0.791, 1-sided P=0.0100).
Researchers said there was an OS benefit with the carfilzomib combination whether or not patients received prior treatment with bortezomib and regardless of patients’ age, ECOG performance status at baseline, cytogenetic risk group, or the number of previous therapies they received.
The HR was 0.75 (carfilzomib vs bortezomib) for patients with no prior bortezomib and 0.84 for patients who received prior bortezomib. The HR was 0.85 for patients younger than 65, 0.71 for those ages 65 to 74, and 0.84 for patients age 75 and older.
The HR was 0.81 for patients with an ECOG status of 0, 0.80 for those with a status of 1, and 0.50 for those with a status of 2. The HR was 0.83 for patients with high-risk cytogenetics and 0.85 for those with standard-risk cytogenetics.
The HR was 0.83 for patients with 1 prior line of therapy and 0.76 for those with 2 to 3 prior lines of therapy.
The researchers said safety results in this analysis were comparable with previously reported results. The incidence of grade 3 or higher adverse events was 81.4% in the carfilzomib arm and 71.1% in the bortezomib arm.
The most common adverse events of any grade (in the carfilzomib and bortezomib arms, respectively) were anemia (42.5% and 28.3%), diarrhea (36.3% and 40.6%), pyrexia (32.4% and 15.4%), dyspnea (32.2% and 13.6%), fatigue (32.2% and 30.7%), and hypertension (32.2% and 9.9%).
Chlormethine gel approved to treat mycosis fungoides
The European Commission has granted marketing authorization for chlormethine gel (Ledaga®) as a treatment for adults with mycosis fungoides (MF), but the product is not expected to be available until next year.
Ledaga is a hybrid medicine of Caryolysine, which has been approved for use in the European Union since 1946.
Hybrid medicines have a different strength, are administered differently, or have a different indication from the reference medicine.
Ledaga contains the same active substance as Caryolysine—chlormethine, a bifunctional alkylating agent that inhibits rapidly proliferating cells—but Ledaga is a gel intended for cutaneous use.
Actelion Pharmaceuticals Ltd, the company developing Ledaga, has agreed to fulfill a list of post-approval measures for the product proposed by the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Subject to fulfilling the agreed commitments and achieving market access in various countries, a potential first European launch of Ledaga is not expected before January 2018. When it is launched, Ledaga will be available as a 160 μg/g gel.
Phase 2 study
The authorization of hybrid medicines depends partly on the results of tests on the reference medicine and partly on new data from clinical trials.
The marketing authorization for Ledaga is based, in part, on results of a multicenter, randomized, observer-blinded, active-controlled study of patients with stage I and IIA MF. Results from this phase 2 study were published in JAMA Dermatology.
The study enrolled 260 MF patients who were randomized 1:1 to receive topical treatment with 0.02% chlormethine gel (Ledaga) or compounded control—0.02% chlormethine compounded in Aquaphor® ointment—once daily for up to 12 months.
A response was defined as at least a 50% improvement in the baseline Composite Assessment of Index Lesion Severity score.
In the intent-to-treat population, 59% (76/130) of patients who received Ledaga achieved a clinical response, compared to 48% (62/130) of patients treated with the compounded control. The rate of complete response was 14% (n=18) and 12% (n=15), respectively.
Patients who were treated for at least 6 months were included in the efficacy-evaluable population. In this population, 77% (69/90) of patients who received Ledaga achieved a clinical response, compared to 59% (56/95) of patients treated with the compounded control. The rate of complete response was 19% (n=17) and 15% (n=14), respectively.
Reductions in mean lesion severity were seen as early as 4 weeks into the study, with further reductions observed with continuing therapy. The time to first confirmed response favored Ledaga.
The most frequent adverse reactions reported with Ledaga were skin-related—dermatitis (55%; eg, skin irritation, erythema, rash, urticaria, skin-burning sensation, skin pain), pruritus (20%), skin infections (12%), skin ulceration and blistering (6%), and skin hyperpigmentation (6%).
No systemic absorption of chlormethine was detected with treatment.
The European Commission has granted marketing authorization for chlormethine gel (Ledaga®) as a treatment for adults with mycosis fungoides (MF), but the product is not expected to be available until next year.
Ledaga is a hybrid medicine of Caryolysine, which has been approved for use in the European Union since 1946.
Hybrid medicines have a different strength, are administered differently, or have a different indication from the reference medicine.
Ledaga contains the same active substance as Caryolysine—chlormethine, a bifunctional alkylating agent that inhibits rapidly proliferating cells—but Ledaga is a gel intended for cutaneous use.
Actelion Pharmaceuticals Ltd, the company developing Ledaga, has agreed to fulfill a list of post-approval measures for the product proposed by the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Subject to fulfilling the agreed commitments and achieving market access in various countries, a potential first European launch of Ledaga is not expected before January 2018. When it is launched, Ledaga will be available as a 160 μg/g gel.
Phase 2 study
The authorization of hybrid medicines depends partly on the results of tests on the reference medicine and partly on new data from clinical trials.
The marketing authorization for Ledaga is based, in part, on results of a multicenter, randomized, observer-blinded, active-controlled study of patients with stage I and IIA MF. Results from this phase 2 study were published in JAMA Dermatology.
The study enrolled 260 MF patients who were randomized 1:1 to receive topical treatment with 0.02% chlormethine gel (Ledaga) or compounded control—0.02% chlormethine compounded in Aquaphor® ointment—once daily for up to 12 months.
A response was defined as at least a 50% improvement in the baseline Composite Assessment of Index Lesion Severity score.
In the intent-to-treat population, 59% (76/130) of patients who received Ledaga achieved a clinical response, compared to 48% (62/130) of patients treated with the compounded control. The rate of complete response was 14% (n=18) and 12% (n=15), respectively.
Patients who were treated for at least 6 months were included in the efficacy-evaluable population. In this population, 77% (69/90) of patients who received Ledaga achieved a clinical response, compared to 59% (56/95) of patients treated with the compounded control. The rate of complete response was 19% (n=17) and 15% (n=14), respectively.
Reductions in mean lesion severity were seen as early as 4 weeks into the study, with further reductions observed with continuing therapy. The time to first confirmed response favored Ledaga.
The most frequent adverse reactions reported with Ledaga were skin-related—dermatitis (55%; eg, skin irritation, erythema, rash, urticaria, skin-burning sensation, skin pain), pruritus (20%), skin infections (12%), skin ulceration and blistering (6%), and skin hyperpigmentation (6%).
No systemic absorption of chlormethine was detected with treatment.
The European Commission has granted marketing authorization for chlormethine gel (Ledaga®) as a treatment for adults with mycosis fungoides (MF), but the product is not expected to be available until next year.
Ledaga is a hybrid medicine of Caryolysine, which has been approved for use in the European Union since 1946.
Hybrid medicines have a different strength, are administered differently, or have a different indication from the reference medicine.
Ledaga contains the same active substance as Caryolysine—chlormethine, a bifunctional alkylating agent that inhibits rapidly proliferating cells—but Ledaga is a gel intended for cutaneous use.
Actelion Pharmaceuticals Ltd, the company developing Ledaga, has agreed to fulfill a list of post-approval measures for the product proposed by the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Subject to fulfilling the agreed commitments and achieving market access in various countries, a potential first European launch of Ledaga is not expected before January 2018. When it is launched, Ledaga will be available as a 160 μg/g gel.
Phase 2 study
The authorization of hybrid medicines depends partly on the results of tests on the reference medicine and partly on new data from clinical trials.
The marketing authorization for Ledaga is based, in part, on results of a multicenter, randomized, observer-blinded, active-controlled study of patients with stage I and IIA MF. Results from this phase 2 study were published in JAMA Dermatology.
The study enrolled 260 MF patients who were randomized 1:1 to receive topical treatment with 0.02% chlormethine gel (Ledaga) or compounded control—0.02% chlormethine compounded in Aquaphor® ointment—once daily for up to 12 months.
A response was defined as at least a 50% improvement in the baseline Composite Assessment of Index Lesion Severity score.
In the intent-to-treat population, 59% (76/130) of patients who received Ledaga achieved a clinical response, compared to 48% (62/130) of patients treated with the compounded control. The rate of complete response was 14% (n=18) and 12% (n=15), respectively.
Patients who were treated for at least 6 months were included in the efficacy-evaluable population. In this population, 77% (69/90) of patients who received Ledaga achieved a clinical response, compared to 59% (56/95) of patients treated with the compounded control. The rate of complete response was 19% (n=17) and 15% (n=14), respectively.
Reductions in mean lesion severity were seen as early as 4 weeks into the study, with further reductions observed with continuing therapy. The time to first confirmed response favored Ledaga.
The most frequent adverse reactions reported with Ledaga were skin-related—dermatitis (55%; eg, skin irritation, erythema, rash, urticaria, skin-burning sensation, skin pain), pruritus (20%), skin infections (12%), skin ulceration and blistering (6%), and skin hyperpigmentation (6%).
No systemic absorption of chlormethine was detected with treatment.
Rising arthritis prevalence driven by obesity
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: The prevalence of arthritis in the general population is growing and increasing obesity appears to be a factor.
Major finding: When researchers used the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Data source: A longitudinal analysis of data from the 1994/95 to 2010/11 National Population Health survey that included 8,817 participants in four birth cohorts.
Disclosures: The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
When Heart Problems Crop Up
ANSWER
This ECG shows a sinus rhythm with premature atrial complexes, a normal axis, a right bundle branch block, and T-wave abnormalities consistent with lateral ischemia.
Sinus rhythm is evidenced by the P waves’ rate of ≥ 60 beats/min and ≤ 100 beats/min. The P waves that indicate premature atrial contractions have a different appearance than normal P waves, a result of the atrial activation from a site other than the sinus node. Because both the normal P wave and the premature atrial contraction conduct through the normal ventricular conduction system, the associated QRS complexes are identica
A right bundle branch block is identified by a QRS duration > 120 ms with a terminal broad S wave in lead I and an RSR’ complex in leads V1 and V2. The ST segment depressions in precordial leads V3 through V6 propagate the diagnosis of lateral ischemia.
The patient was not found to have atrial fibrillation, and his palpitations and evidence of lateral ischemia resolved when he resumed taking his ß-blocker.
ANSWER
This ECG shows a sinus rhythm with premature atrial complexes, a normal axis, a right bundle branch block, and T-wave abnormalities consistent with lateral ischemia.
Sinus rhythm is evidenced by the P waves’ rate of ≥ 60 beats/min and ≤ 100 beats/min. The P waves that indicate premature atrial contractions have a different appearance than normal P waves, a result of the atrial activation from a site other than the sinus node. Because both the normal P wave and the premature atrial contraction conduct through the normal ventricular conduction system, the associated QRS complexes are identica
A right bundle branch block is identified by a QRS duration > 120 ms with a terminal broad S wave in lead I and an RSR’ complex in leads V1 and V2. The ST segment depressions in precordial leads V3 through V6 propagate the diagnosis of lateral ischemia.
The patient was not found to have atrial fibrillation, and his palpitations and evidence of lateral ischemia resolved when he resumed taking his ß-blocker.
ANSWER
This ECG shows a sinus rhythm with premature atrial complexes, a normal axis, a right bundle branch block, and T-wave abnormalities consistent with lateral ischemia.
Sinus rhythm is evidenced by the P waves’ rate of ≥ 60 beats/min and ≤ 100 beats/min. The P waves that indicate premature atrial contractions have a different appearance than normal P waves, a result of the atrial activation from a site other than the sinus node. Because both the normal P wave and the premature atrial contraction conduct through the normal ventricular conduction system, the associated QRS complexes are identica
A right bundle branch block is identified by a QRS duration > 120 ms with a terminal broad S wave in lead I and an RSR’ complex in leads V1 and V2. The ST segment depressions in precordial leads V3 through V6 propagate the diagnosis of lateral ischemia.
The patient was not found to have atrial fibrillation, and his palpitations and evidence of lateral ischemia resolved when he resumed taking his ß-blocker.
A 72-year-old farmer presents with heart palpitations he has had for the past three weeks. He fears he may be in atrial fibrillation and at risk for a stroke, stating that a few months ago his neighbor complained of palpitations (later attributed to atrial fibrillation) and had an embolic stroke due to a clot in the left atrium. The patient denies any history of cardiac arrhythmias, chest pain, syncope, or near-syncope. He does report occasional bouts of lightheadedness, which have increased in frequency. He is more concerned, though, by the strong, intensified heartbeats that he can feel in his throat.
Past medical and surgical histories are positive for type 2 diabetes, hypertension, and hyperlipidemia, as well as an appendectomy and cholecystectomy. He has also had several upper extremity fractures in the past, all of which have healed well.
The patient’s wife died recently from complications following a hip replacement surgery, but he and his two sons continue to work on the 460-acre family farm he has owned all his life. A chronic smoker, he has smoked one to two packs of cigarettes per day since he was 15. He does not drink alcohol but does consume one to two pots of coffee per day.
His medication list includes metformin, atorvastatin, and metoprolol. He hasn’t taken his metoprolol for two months, because he switched pharmacies and the pills he received were a different color so he didn’t believe they were the right drug (despite the label on the bottle). He has no known drug allergies, but sulfa drugs induce nausea.
The review of systems is remarkable for arthritic pain in his hands, shoulders, hips, knees, and ankles. The patient complains of gastric reflux and occasional diarrhea. He states his mood is still down from the loss of his wife, but he denies being depressed.
His weight is 232 lb and his height, 70 in. Vital signs include a blood pressure of 168/92 mm Hg; pulse, 84 beats/min; respiratory rate, 14 breaths/min-1; and temperature, 99.2°F.
Physical exam reveals a weathered but otherwise healthy-looking male in no distress. He wears corrective lenses. The HEENT exam reveals surprisingly good dentition for a man his age. There are no carotid bruits. The lungs have expiratory crackles in both bases that change with coughing.
The cardiac exam reveals an irregular rate of 88 beats/min with a grade II/VI early systolic murmur at the left upper sternal border. There are no extra heart sounds or rubs. The abdomen is soft and nontender with old, well-healed cholecystectomy and appendectomy incision scars. The peripheral pulses are strong and equal bilaterally. Arthritic changes are evident in the hands and feet. The neurologic exam is grossly intact.
An ECG is performed; it reveals a ventricular rate of 87 beats/min; PR interval, 156 ms; QRS duration, 138 ms; QT/QTc interval, 440/529 ms; P axis, 58°; R axis, 26°; and T axis, 105°. What is your interpretation of this ECG?
Sneak Peek: The Hospital Leader Blog
Editor’s note: This article first appeared on “The Hospital Leader” blog. Read the full post at hospitalleader.org.
In December, I wrote a letter to hospital executives, urging them to deliberately invest their own personal time and effort in fostering hospitalist well-being. I suggested several actions that leaders can take to enhance hospitalist job satisfaction and reduce the risk of burnout and turnover.
Following publication of that post, I heard from several hospital executives and was pleasantly surprised that they all responded positively to my message. Several execs told me that they gained valuable new insights about their hospitalists’ challenges and needs; others said they planned to take action on one or more of my suggestions that had never occurred to them before.
Their feedback reinforced my belief that most hospital leaders actually do care a lot about promoting healthy, stable, and sustainable hospitalist programs, but the hospital leaders I talked with also had some messages for their hospitalist colleagues, and I think it’s important to share them in the spirit of fostering a healthy exchange of perspectives. Your hospital’s leaders would be delighted and encouraged if you engaged them in dialogue about these issues.
Help us help you
Several hospital leaders told me that their hospitalists grumble about being treated by the medical staff (and even nurses) like second-class citizens or glorified residents. Those same hospitalists, however, routinely show up for work dressed in scrubs and tennis shoes rather than professional attire. They rarely come in early when it’s busy or invest more time than is absolutely needed to see the patients on their list, making it easy for others to dismiss them as shift workers.
Hospitalists, they say, are unwilling to come in on their own time to attend a medical staff meeting, something other doctors do as a matter of course. And instead of interacting as social peers with other physicians when opportunity arises (i.e., in the cafeteria or doctors’ lounge), the hospitalists just grab food and head back to eat together in their work room.
The executives said they want to help enhance the stature of their hospitalists within the medical staff, but the Here’s a typical comment:
“[Hospitalists] also need to be willing to participate in hospital and system committees. Although this may require them to interrupt their workflow and stay late on some days they are working or come in on days off, they will never garner the respect of their colleagues if they are unwilling to do so.”
Read the full post at hospitalleader.org.
Leslie Flores is a hospital medicine consultant and member of SHM’s Practice Analysis Committee.
Also on The Hospital Leader. . .
• Creating Value through Crowdsourcing & Finding ‘Value’ in the New Year, by Vineet Arora, MD, MPP, FHM
• BREAKING NEWS: “Physicians Deemed Unnecessary”; Social Worker Promoted to Hospital CEO, by Jordan Messler, MD, SFHM
• ER Docs and Out-of-Network Billing: Are We in the Same Boat?, by Brad Flansbaum, DO, MPH, MHM
• The Best Way to Die?, by David Brabeck, MD
Editor’s note: This article first appeared on “The Hospital Leader” blog. Read the full post at hospitalleader.org.
In December, I wrote a letter to hospital executives, urging them to deliberately invest their own personal time and effort in fostering hospitalist well-being. I suggested several actions that leaders can take to enhance hospitalist job satisfaction and reduce the risk of burnout and turnover.
Following publication of that post, I heard from several hospital executives and was pleasantly surprised that they all responded positively to my message. Several execs told me that they gained valuable new insights about their hospitalists’ challenges and needs; others said they planned to take action on one or more of my suggestions that had never occurred to them before.
Their feedback reinforced my belief that most hospital leaders actually do care a lot about promoting healthy, stable, and sustainable hospitalist programs, but the hospital leaders I talked with also had some messages for their hospitalist colleagues, and I think it’s important to share them in the spirit of fostering a healthy exchange of perspectives. Your hospital’s leaders would be delighted and encouraged if you engaged them in dialogue about these issues.
Help us help you
Several hospital leaders told me that their hospitalists grumble about being treated by the medical staff (and even nurses) like second-class citizens or glorified residents. Those same hospitalists, however, routinely show up for work dressed in scrubs and tennis shoes rather than professional attire. They rarely come in early when it’s busy or invest more time than is absolutely needed to see the patients on their list, making it easy for others to dismiss them as shift workers.
Hospitalists, they say, are unwilling to come in on their own time to attend a medical staff meeting, something other doctors do as a matter of course. And instead of interacting as social peers with other physicians when opportunity arises (i.e., in the cafeteria or doctors’ lounge), the hospitalists just grab food and head back to eat together in their work room.
The executives said they want to help enhance the stature of their hospitalists within the medical staff, but the Here’s a typical comment:
“[Hospitalists] also need to be willing to participate in hospital and system committees. Although this may require them to interrupt their workflow and stay late on some days they are working or come in on days off, they will never garner the respect of their colleagues if they are unwilling to do so.”
Read the full post at hospitalleader.org.
Leslie Flores is a hospital medicine consultant and member of SHM’s Practice Analysis Committee.
Also on The Hospital Leader. . .
• Creating Value through Crowdsourcing & Finding ‘Value’ in the New Year, by Vineet Arora, MD, MPP, FHM
• BREAKING NEWS: “Physicians Deemed Unnecessary”; Social Worker Promoted to Hospital CEO, by Jordan Messler, MD, SFHM
• ER Docs and Out-of-Network Billing: Are We in the Same Boat?, by Brad Flansbaum, DO, MPH, MHM
• The Best Way to Die?, by David Brabeck, MD
Editor’s note: This article first appeared on “The Hospital Leader” blog. Read the full post at hospitalleader.org.
In December, I wrote a letter to hospital executives, urging them to deliberately invest their own personal time and effort in fostering hospitalist well-being. I suggested several actions that leaders can take to enhance hospitalist job satisfaction and reduce the risk of burnout and turnover.
Following publication of that post, I heard from several hospital executives and was pleasantly surprised that they all responded positively to my message. Several execs told me that they gained valuable new insights about their hospitalists’ challenges and needs; others said they planned to take action on one or more of my suggestions that had never occurred to them before.
Their feedback reinforced my belief that most hospital leaders actually do care a lot about promoting healthy, stable, and sustainable hospitalist programs, but the hospital leaders I talked with also had some messages for their hospitalist colleagues, and I think it’s important to share them in the spirit of fostering a healthy exchange of perspectives. Your hospital’s leaders would be delighted and encouraged if you engaged them in dialogue about these issues.
Help us help you
Several hospital leaders told me that their hospitalists grumble about being treated by the medical staff (and even nurses) like second-class citizens or glorified residents. Those same hospitalists, however, routinely show up for work dressed in scrubs and tennis shoes rather than professional attire. They rarely come in early when it’s busy or invest more time than is absolutely needed to see the patients on their list, making it easy for others to dismiss them as shift workers.
Hospitalists, they say, are unwilling to come in on their own time to attend a medical staff meeting, something other doctors do as a matter of course. And instead of interacting as social peers with other physicians when opportunity arises (i.e., in the cafeteria or doctors’ lounge), the hospitalists just grab food and head back to eat together in their work room.
The executives said they want to help enhance the stature of their hospitalists within the medical staff, but the Here’s a typical comment:
“[Hospitalists] also need to be willing to participate in hospital and system committees. Although this may require them to interrupt their workflow and stay late on some days they are working or come in on days off, they will never garner the respect of their colleagues if they are unwilling to do so.”
Read the full post at hospitalleader.org.
Leslie Flores is a hospital medicine consultant and member of SHM’s Practice Analysis Committee.
Also on The Hospital Leader. . .
• Creating Value through Crowdsourcing & Finding ‘Value’ in the New Year, by Vineet Arora, MD, MPP, FHM
• BREAKING NEWS: “Physicians Deemed Unnecessary”; Social Worker Promoted to Hospital CEO, by Jordan Messler, MD, SFHM
• ER Docs and Out-of-Network Billing: Are We in the Same Boat?, by Brad Flansbaum, DO, MPH, MHM
• The Best Way to Die?, by David Brabeck, MD
New Trump travel order could disrupt meetings, trainees
President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.
The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.
The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.
The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.
“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”
The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”
When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.
The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.
A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.
The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.
“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.
This article was updated March 8, 2017.
[email protected]
On Twitter @legal_med
President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.
The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.
The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.
The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.
“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”
The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”
When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.
The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.
A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.
The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.
“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.
This article was updated March 8, 2017.
[email protected]
On Twitter @legal_med
President’s Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and impede assemblies of the world’s top medical experts.
The executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The new executive measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban that has been blocked by federal courts.
The new order clarifies that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition.
The revised travel ban could disrupt the exchange of medical knowledge by barring foreign experts from traveling to medical and scientific conferences in the United States, and leaves the status of medical trainees from those countries in limbo, according to American Medical Association President Andrew W. Gurman, MD.
“Hundreds of physicians from six countries are subject to the revised executive order and have applied to U.S. training programs and requested visa sponsorship,” he said in a statement. “The new executive order leaves them in limbo and without an explicit waiver, these foreign physicians will be unable to provide care in the U.S. when training programs begin on July 1.”
The new order is already being challenged in court. On March 7, the state of Hawaii filed a lawsuit seeking to block the order, saying that it subjects a portion of Hawaii’s population to “discrimination and second-class treatment.”
When the original ban took effect, thousands of academics from around the world, including physicians, researchers, and professors, vowed to boycott U.S.-based conferences. A Google Docs petition started shortly after the ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.
The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said.
A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9th U.S. Circuit Court of Appeals on Feb. 9.
The new executive order excludes Iraq this time around and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.
“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.
This article was updated March 8, 2017.
[email protected]
On Twitter @legal_med
House Republicans start work on ACA repeal/replace
House Republicans have formally begun their efforts to repeal and replace the Affordable Care Act, but a group of four GOP senators could present a significant hurdle to getting the budget reconciliation package to the president’s desk.
The budget reconciliation language – introduced March 6 – represents the first of three phases in their planned effort to quash the ACA.
“Second are all the regulatory modifications and changes that can be put into place,” Dr. Price said, noting that the Obama administration made 192 specific rules related to the ACA and published more than 5,000 letters of guidance. “We are going to go through every single one of those and ... if they help patients, we need to continue them. If they harm patients or increase costs, they need to be addressed.”
He added that additional legislation could be needed to address changes that cannot be made through the reconciliation process, such as addressing prescription drug costs and allowing health insurance to be sold across state lines.
Sections of the reconciliation package were introduced in the House Energy and Commerce and House Ways and Means Committees, covering areas relative to each committee’s jurisdiction. Taken together, they put forth the plan to repeal and replace certain revenue aspects of the ACA.
Provisions to repeal Medicaid expansion likely will prove the most problematic. The Energy and Commerce language calls for the repeal of Medicaid expansion provisions by 2020. It also repeals a requirement that state Medicaid plans offer the same minimum essential health benefits that are required by plans on the exchanges.
Starting in fiscal 2020, states would begin to receive a per capita allotment to fund their Medicaid programs, a fixed amount per Medicaid enrollee that will adjust over time for inflation using the consumer price index. States spending more than their annual allotment per beneficiary would be penalized with reduced funding in the following year.
That provision has run afoul of certain Republican senators whose votes are needed to gain a simple majority and pass the budget reconciliation package. Because of the slim nature of the Republican majority, any defection from the party line could endanger passage.
“We are concerned that any poorly implemented or poorly timed change in the current funding structure in Medicaid could result in a reduction in access to life-saving health care services,” Sen. Rob Portman (R-Ohio), Sen. Shelley Moore Capito (R-W.Va.), Sen. Cory Gardner (R-Colo.), and Sen. Lisa Murkowski (R-Alaska) said in a letter to Senate Majority Leader Mitch McConnell (R-Ky.). The letter was based on an earlier draft of the legislative language but remains valid as little substantive change has occurred in the formal, introduced language.
“We believe Medicaid needs to be reformed, but reform should not come at the cost of disruption in access to health care for our country’s most vulnerable and sickest individuals,” the senators continued. “Any changes made to how Medicaid is financed through the state and federal governments should be coupled with significant new flexibility so they can efficiently and effectively manage their Medicaid programs to best meet their own needs. ... [The House proposal] does not meet the test of stability for individuals currently enrolled in the program, and we will not support a plan that does not include stability for Medicaid expansion populations or flexibility for states.”
The Energy and Commerce language also includes provisions for block grants to states that would allow them to be used in a manner they see fit within a defined list, including providing financial assistance to high-risk individuals; arrangements that help stabilize premiums in the individual market; reduce the cost of providing insurance in the small group and individual markets; promoting participation in the small group and individual markets; and promoting access to preventive, dental, and vision services as well as treatment for mental and substance abuse disorders. Funds could also be used to provide payments for care or assistance to reduce out-of-pocket costs.
The House proposal also would repeal the premium cost sharing subsidies in the ACA, which would be replaced with refundable tax credits, according to the language released by the Ways and Means Committee.
The credit can be used to purchase a state-approved, major health insurance or unsubsidized COBRA (the Consolidated Omnibus Budget Reconciliation Act) coverage and increases based on age. Individuals younger than age 30 years would get $2,000, and the credit increases in $500 increments per 10-year age block, plateauing at $4,000 for those aged 60 years and older. The caps will adjust over time, based on inflation, and are available to those making up to $75,000 ($150,000 for joint filers); the credit phases out by $100 for every $1,000 over those thresholds.
The Ways and Means language also repeals a number of revenue provisions, including the individual mandate and associated penalties; the employer mandate and associated penalties; taxes on high-cost health plans (Cadillac tax); over-the-counter and prescription medications; health savings accounts; tanning; investment; and on health insurers.
In place of the individual mandate, the language will allow insurers to raise premiums by up to 30%.
The bill does not repeal the provisions regarding young adults being able to stay on their parents’ policies to the age of 26 years, nor does it allow insurers to deny coverage for preexisting conditions.
The House committees will begin consideration of their respective languages on March 8.
House Republicans have formally begun their efforts to repeal and replace the Affordable Care Act, but a group of four GOP senators could present a significant hurdle to getting the budget reconciliation package to the president’s desk.
The budget reconciliation language – introduced March 6 – represents the first of three phases in their planned effort to quash the ACA.
“Second are all the regulatory modifications and changes that can be put into place,” Dr. Price said, noting that the Obama administration made 192 specific rules related to the ACA and published more than 5,000 letters of guidance. “We are going to go through every single one of those and ... if they help patients, we need to continue them. If they harm patients or increase costs, they need to be addressed.”
He added that additional legislation could be needed to address changes that cannot be made through the reconciliation process, such as addressing prescription drug costs and allowing health insurance to be sold across state lines.
Sections of the reconciliation package were introduced in the House Energy and Commerce and House Ways and Means Committees, covering areas relative to each committee’s jurisdiction. Taken together, they put forth the plan to repeal and replace certain revenue aspects of the ACA.
Provisions to repeal Medicaid expansion likely will prove the most problematic. The Energy and Commerce language calls for the repeal of Medicaid expansion provisions by 2020. It also repeals a requirement that state Medicaid plans offer the same minimum essential health benefits that are required by plans on the exchanges.
Starting in fiscal 2020, states would begin to receive a per capita allotment to fund their Medicaid programs, a fixed amount per Medicaid enrollee that will adjust over time for inflation using the consumer price index. States spending more than their annual allotment per beneficiary would be penalized with reduced funding in the following year.
That provision has run afoul of certain Republican senators whose votes are needed to gain a simple majority and pass the budget reconciliation package. Because of the slim nature of the Republican majority, any defection from the party line could endanger passage.
“We are concerned that any poorly implemented or poorly timed change in the current funding structure in Medicaid could result in a reduction in access to life-saving health care services,” Sen. Rob Portman (R-Ohio), Sen. Shelley Moore Capito (R-W.Va.), Sen. Cory Gardner (R-Colo.), and Sen. Lisa Murkowski (R-Alaska) said in a letter to Senate Majority Leader Mitch McConnell (R-Ky.). The letter was based on an earlier draft of the legislative language but remains valid as little substantive change has occurred in the formal, introduced language.
“We believe Medicaid needs to be reformed, but reform should not come at the cost of disruption in access to health care for our country’s most vulnerable and sickest individuals,” the senators continued. “Any changes made to how Medicaid is financed through the state and federal governments should be coupled with significant new flexibility so they can efficiently and effectively manage their Medicaid programs to best meet their own needs. ... [The House proposal] does not meet the test of stability for individuals currently enrolled in the program, and we will not support a plan that does not include stability for Medicaid expansion populations or flexibility for states.”
The Energy and Commerce language also includes provisions for block grants to states that would allow them to be used in a manner they see fit within a defined list, including providing financial assistance to high-risk individuals; arrangements that help stabilize premiums in the individual market; reduce the cost of providing insurance in the small group and individual markets; promoting participation in the small group and individual markets; and promoting access to preventive, dental, and vision services as well as treatment for mental and substance abuse disorders. Funds could also be used to provide payments for care or assistance to reduce out-of-pocket costs.
The House proposal also would repeal the premium cost sharing subsidies in the ACA, which would be replaced with refundable tax credits, according to the language released by the Ways and Means Committee.
The credit can be used to purchase a state-approved, major health insurance or unsubsidized COBRA (the Consolidated Omnibus Budget Reconciliation Act) coverage and increases based on age. Individuals younger than age 30 years would get $2,000, and the credit increases in $500 increments per 10-year age block, plateauing at $4,000 for those aged 60 years and older. The caps will adjust over time, based on inflation, and are available to those making up to $75,000 ($150,000 for joint filers); the credit phases out by $100 for every $1,000 over those thresholds.
The Ways and Means language also repeals a number of revenue provisions, including the individual mandate and associated penalties; the employer mandate and associated penalties; taxes on high-cost health plans (Cadillac tax); over-the-counter and prescription medications; health savings accounts; tanning; investment; and on health insurers.
In place of the individual mandate, the language will allow insurers to raise premiums by up to 30%.
The bill does not repeal the provisions regarding young adults being able to stay on their parents’ policies to the age of 26 years, nor does it allow insurers to deny coverage for preexisting conditions.
The House committees will begin consideration of their respective languages on March 8.
House Republicans have formally begun their efforts to repeal and replace the Affordable Care Act, but a group of four GOP senators could present a significant hurdle to getting the budget reconciliation package to the president’s desk.
The budget reconciliation language – introduced March 6 – represents the first of three phases in their planned effort to quash the ACA.
“Second are all the regulatory modifications and changes that can be put into place,” Dr. Price said, noting that the Obama administration made 192 specific rules related to the ACA and published more than 5,000 letters of guidance. “We are going to go through every single one of those and ... if they help patients, we need to continue them. If they harm patients or increase costs, they need to be addressed.”
He added that additional legislation could be needed to address changes that cannot be made through the reconciliation process, such as addressing prescription drug costs and allowing health insurance to be sold across state lines.
Sections of the reconciliation package were introduced in the House Energy and Commerce and House Ways and Means Committees, covering areas relative to each committee’s jurisdiction. Taken together, they put forth the plan to repeal and replace certain revenue aspects of the ACA.
Provisions to repeal Medicaid expansion likely will prove the most problematic. The Energy and Commerce language calls for the repeal of Medicaid expansion provisions by 2020. It also repeals a requirement that state Medicaid plans offer the same minimum essential health benefits that are required by plans on the exchanges.
Starting in fiscal 2020, states would begin to receive a per capita allotment to fund their Medicaid programs, a fixed amount per Medicaid enrollee that will adjust over time for inflation using the consumer price index. States spending more than their annual allotment per beneficiary would be penalized with reduced funding in the following year.
That provision has run afoul of certain Republican senators whose votes are needed to gain a simple majority and pass the budget reconciliation package. Because of the slim nature of the Republican majority, any defection from the party line could endanger passage.
“We are concerned that any poorly implemented or poorly timed change in the current funding structure in Medicaid could result in a reduction in access to life-saving health care services,” Sen. Rob Portman (R-Ohio), Sen. Shelley Moore Capito (R-W.Va.), Sen. Cory Gardner (R-Colo.), and Sen. Lisa Murkowski (R-Alaska) said in a letter to Senate Majority Leader Mitch McConnell (R-Ky.). The letter was based on an earlier draft of the legislative language but remains valid as little substantive change has occurred in the formal, introduced language.
“We believe Medicaid needs to be reformed, but reform should not come at the cost of disruption in access to health care for our country’s most vulnerable and sickest individuals,” the senators continued. “Any changes made to how Medicaid is financed through the state and federal governments should be coupled with significant new flexibility so they can efficiently and effectively manage their Medicaid programs to best meet their own needs. ... [The House proposal] does not meet the test of stability for individuals currently enrolled in the program, and we will not support a plan that does not include stability for Medicaid expansion populations or flexibility for states.”
The Energy and Commerce language also includes provisions for block grants to states that would allow them to be used in a manner they see fit within a defined list, including providing financial assistance to high-risk individuals; arrangements that help stabilize premiums in the individual market; reduce the cost of providing insurance in the small group and individual markets; promoting participation in the small group and individual markets; and promoting access to preventive, dental, and vision services as well as treatment for mental and substance abuse disorders. Funds could also be used to provide payments for care or assistance to reduce out-of-pocket costs.
The House proposal also would repeal the premium cost sharing subsidies in the ACA, which would be replaced with refundable tax credits, according to the language released by the Ways and Means Committee.
The credit can be used to purchase a state-approved, major health insurance or unsubsidized COBRA (the Consolidated Omnibus Budget Reconciliation Act) coverage and increases based on age. Individuals younger than age 30 years would get $2,000, and the credit increases in $500 increments per 10-year age block, plateauing at $4,000 for those aged 60 years and older. The caps will adjust over time, based on inflation, and are available to those making up to $75,000 ($150,000 for joint filers); the credit phases out by $100 for every $1,000 over those thresholds.
The Ways and Means language also repeals a number of revenue provisions, including the individual mandate and associated penalties; the employer mandate and associated penalties; taxes on high-cost health plans (Cadillac tax); over-the-counter and prescription medications; health savings accounts; tanning; investment; and on health insurers.
In place of the individual mandate, the language will allow insurers to raise premiums by up to 30%.
The bill does not repeal the provisions regarding young adults being able to stay on their parents’ policies to the age of 26 years, nor does it allow insurers to deny coverage for preexisting conditions.
The House committees will begin consideration of their respective languages on March 8.
CDC: Greater activity limitations accompany rising arthritis prevalence
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
FROM MMWR
Key clinical point:
Major finding: About 24 million American adults report being significantly limited due to their arthritis.
Data source: 2013-2015 data from the National Health Interview Survey.
Disclosures: No disclosures were reported.
Depression and deep brain stimulation: ‘Furor therapeuticus redux’
Looking back after a long and distinguished career, Leon Eisenberg, MD, invoked the term “furor therapeuticus” to describe overzealous treatment by doctors who became frustrated with therapeutic limitations or motivated by professional enthusiasm.1
With this in mind, Dr. Eisenberg criticized expansive marketing and prescribing of psychotropic drugs in an editorial published exactly 10 years ago. He might also have questioned the current interest in deep brain stimulation (DBS) as a treatment for depression and a growing list of behavioral disorders. Initial studies of DBS in depression were promising, but recent setbacks have brought research to a scientific and ethical crossroads that compels broader discussion.
Besides uncertainties over the right targets to stimulate, identification of the right candidates for DBS treatment can be difficult. Trials of DBS recruited highly selected depressed subjects with no consensus on symptoms or biomarkers that could be used to predict who might respond. Doctors still rely on clinical symptoms to distinguish patients with melancholic depression, who respond to medications or electroconvulsive therapy and might also respond to DBS, from patients with depressed mood because of psychosocial problems, who respond to psychotherapy or social interventions.
Evidence on the efficacy and safety of DBS in depression is mixed. Initial open trials were promising, with dramatic and sustained recovery in some patients, but they were limited by small numbers of subjects and a lack of randomized controls and standardized methods.4,5
DBS is not without serious side effects, and substantial maintenance costs are not always covered by insurance. So, two recent industry trials were eagerly anticipated but showed no significant differences between active and sham stimulations in depression.6,7 These disappointing results prompted soul-searching among investigators, who presented ingenious ideas for correcting shortcomings that could be tested in future trials but also raised doubts as to the prospects of DBS in depression.4,5
Given that DBS devices already are marketed for neurological disorders, regulation of practice is crucial to prevent off-label misuse in behavioral disorders.8 Federal agencies enforce rules governing DBS devices but rely on investigators and local review boards in research and on voluntary postmarketing reports by individual practitioners to monitor compliance and safety. Unscrupulous commercial interests could expand the market for these devices, as demonstrated by the proliferation of psychotropic drug prescribing decried by Dr. Eisenberg. DBS also must be restricted to specialized teams and medical centers to prevent inappropriate implantation by poorly trained providers.
Because behavioral disorders exact an enormous toll on patients, families, and society, better access to effective care and the search for better treatments must remain public health priorities.
Transformative, breakthrough discoveries in brain research will undoubtedly lead to improvements in treatment, including surgical devices in some cases, but, DBS is at risk of being exaggerated and oversold. Adverse consequences of misuse could provoke a public backlash that would have a chilling effect on vital brain research.
One possible way to prevent this is the risk evaluation and mitigation strategy established by the Food and Drug Administration to manage high-risk pharmaceuticals. The FDA mandates that certain high-risk drugs can be prescribed only if doctors are certified and only if patients are enrolled in a national registry where eligibility, course, and outcome are monitored. A similar mechanism should apply to high-risk surgical devices when used for behavioral disorders.9,10
People with behavioral disorders deserve the right to volunteer for experimental programs that offer hope of recovery for themselves and future generations, but they also deserve to be treated with the utmost scientific rigor and protection that society can provide.
Dr. Caroff is emeritus professor of psychiatry at the University of Pennsylvania, Philadelphia. He has received research grant funding from Sunovion Pharmaceuticals and serves as a consultant to Neurocrine Biosciences and TEVA.
References
1. Am J Psychiatry. 2007;164(4):552-5
2. Curr Behav Neurosci Rep. 2014;1(2):55-63
3. J Affect Disord. 2014;156:1-7
4. JAMA Psychiatry. 2016;739(5):439-40
5. Biol Psychiatry. 2016;79(4):e9-10
6. Stereotact Funct Neurosurg. 2015;93:366-9
7. Neurotherapeutics. 2014;11(3):475-84
8. J Neurol Neurosurg Psychiatry. 2014;85(9):1003-8
9. Brain Stimul. 2012;5(4):653-5
10. Fed Reg. 1977 May 23;42(99):26318-32
Looking back after a long and distinguished career, Leon Eisenberg, MD, invoked the term “furor therapeuticus” to describe overzealous treatment by doctors who became frustrated with therapeutic limitations or motivated by professional enthusiasm.1
With this in mind, Dr. Eisenberg criticized expansive marketing and prescribing of psychotropic drugs in an editorial published exactly 10 years ago. He might also have questioned the current interest in deep brain stimulation (DBS) as a treatment for depression and a growing list of behavioral disorders. Initial studies of DBS in depression were promising, but recent setbacks have brought research to a scientific and ethical crossroads that compels broader discussion.
Besides uncertainties over the right targets to stimulate, identification of the right candidates for DBS treatment can be difficult. Trials of DBS recruited highly selected depressed subjects with no consensus on symptoms or biomarkers that could be used to predict who might respond. Doctors still rely on clinical symptoms to distinguish patients with melancholic depression, who respond to medications or electroconvulsive therapy and might also respond to DBS, from patients with depressed mood because of psychosocial problems, who respond to psychotherapy or social interventions.
Evidence on the efficacy and safety of DBS in depression is mixed. Initial open trials were promising, with dramatic and sustained recovery in some patients, but they were limited by small numbers of subjects and a lack of randomized controls and standardized methods.4,5
DBS is not without serious side effects, and substantial maintenance costs are not always covered by insurance. So, two recent industry trials were eagerly anticipated but showed no significant differences between active and sham stimulations in depression.6,7 These disappointing results prompted soul-searching among investigators, who presented ingenious ideas for correcting shortcomings that could be tested in future trials but also raised doubts as to the prospects of DBS in depression.4,5
Given that DBS devices already are marketed for neurological disorders, regulation of practice is crucial to prevent off-label misuse in behavioral disorders.8 Federal agencies enforce rules governing DBS devices but rely on investigators and local review boards in research and on voluntary postmarketing reports by individual practitioners to monitor compliance and safety. Unscrupulous commercial interests could expand the market for these devices, as demonstrated by the proliferation of psychotropic drug prescribing decried by Dr. Eisenberg. DBS also must be restricted to specialized teams and medical centers to prevent inappropriate implantation by poorly trained providers.
Because behavioral disorders exact an enormous toll on patients, families, and society, better access to effective care and the search for better treatments must remain public health priorities.
Transformative, breakthrough discoveries in brain research will undoubtedly lead to improvements in treatment, including surgical devices in some cases, but, DBS is at risk of being exaggerated and oversold. Adverse consequences of misuse could provoke a public backlash that would have a chilling effect on vital brain research.
One possible way to prevent this is the risk evaluation and mitigation strategy established by the Food and Drug Administration to manage high-risk pharmaceuticals. The FDA mandates that certain high-risk drugs can be prescribed only if doctors are certified and only if patients are enrolled in a national registry where eligibility, course, and outcome are monitored. A similar mechanism should apply to high-risk surgical devices when used for behavioral disorders.9,10
People with behavioral disorders deserve the right to volunteer for experimental programs that offer hope of recovery for themselves and future generations, but they also deserve to be treated with the utmost scientific rigor and protection that society can provide.
Dr. Caroff is emeritus professor of psychiatry at the University of Pennsylvania, Philadelphia. He has received research grant funding from Sunovion Pharmaceuticals and serves as a consultant to Neurocrine Biosciences and TEVA.
References
1. Am J Psychiatry. 2007;164(4):552-5
2. Curr Behav Neurosci Rep. 2014;1(2):55-63
3. J Affect Disord. 2014;156:1-7
4. JAMA Psychiatry. 2016;739(5):439-40
5. Biol Psychiatry. 2016;79(4):e9-10
6. Stereotact Funct Neurosurg. 2015;93:366-9
7. Neurotherapeutics. 2014;11(3):475-84
8. J Neurol Neurosurg Psychiatry. 2014;85(9):1003-8
9. Brain Stimul. 2012;5(4):653-5
10. Fed Reg. 1977 May 23;42(99):26318-32
Looking back after a long and distinguished career, Leon Eisenberg, MD, invoked the term “furor therapeuticus” to describe overzealous treatment by doctors who became frustrated with therapeutic limitations or motivated by professional enthusiasm.1
With this in mind, Dr. Eisenberg criticized expansive marketing and prescribing of psychotropic drugs in an editorial published exactly 10 years ago. He might also have questioned the current interest in deep brain stimulation (DBS) as a treatment for depression and a growing list of behavioral disorders. Initial studies of DBS in depression were promising, but recent setbacks have brought research to a scientific and ethical crossroads that compels broader discussion.
Besides uncertainties over the right targets to stimulate, identification of the right candidates for DBS treatment can be difficult. Trials of DBS recruited highly selected depressed subjects with no consensus on symptoms or biomarkers that could be used to predict who might respond. Doctors still rely on clinical symptoms to distinguish patients with melancholic depression, who respond to medications or electroconvulsive therapy and might also respond to DBS, from patients with depressed mood because of psychosocial problems, who respond to psychotherapy or social interventions.
Evidence on the efficacy and safety of DBS in depression is mixed. Initial open trials were promising, with dramatic and sustained recovery in some patients, but they were limited by small numbers of subjects and a lack of randomized controls and standardized methods.4,5
DBS is not without serious side effects, and substantial maintenance costs are not always covered by insurance. So, two recent industry trials were eagerly anticipated but showed no significant differences between active and sham stimulations in depression.6,7 These disappointing results prompted soul-searching among investigators, who presented ingenious ideas for correcting shortcomings that could be tested in future trials but also raised doubts as to the prospects of DBS in depression.4,5
Given that DBS devices already are marketed for neurological disorders, regulation of practice is crucial to prevent off-label misuse in behavioral disorders.8 Federal agencies enforce rules governing DBS devices but rely on investigators and local review boards in research and on voluntary postmarketing reports by individual practitioners to monitor compliance and safety. Unscrupulous commercial interests could expand the market for these devices, as demonstrated by the proliferation of psychotropic drug prescribing decried by Dr. Eisenberg. DBS also must be restricted to specialized teams and medical centers to prevent inappropriate implantation by poorly trained providers.
Because behavioral disorders exact an enormous toll on patients, families, and society, better access to effective care and the search for better treatments must remain public health priorities.
Transformative, breakthrough discoveries in brain research will undoubtedly lead to improvements in treatment, including surgical devices in some cases, but, DBS is at risk of being exaggerated and oversold. Adverse consequences of misuse could provoke a public backlash that would have a chilling effect on vital brain research.
One possible way to prevent this is the risk evaluation and mitigation strategy established by the Food and Drug Administration to manage high-risk pharmaceuticals. The FDA mandates that certain high-risk drugs can be prescribed only if doctors are certified and only if patients are enrolled in a national registry where eligibility, course, and outcome are monitored. A similar mechanism should apply to high-risk surgical devices when used for behavioral disorders.9,10
People with behavioral disorders deserve the right to volunteer for experimental programs that offer hope of recovery for themselves and future generations, but they also deserve to be treated with the utmost scientific rigor and protection that society can provide.
Dr. Caroff is emeritus professor of psychiatry at the University of Pennsylvania, Philadelphia. He has received research grant funding from Sunovion Pharmaceuticals and serves as a consultant to Neurocrine Biosciences and TEVA.
References
1. Am J Psychiatry. 2007;164(4):552-5
2. Curr Behav Neurosci Rep. 2014;1(2):55-63
3. J Affect Disord. 2014;156:1-7
4. JAMA Psychiatry. 2016;739(5):439-40
5. Biol Psychiatry. 2016;79(4):e9-10
6. Stereotact Funct Neurosurg. 2015;93:366-9
7. Neurotherapeutics. 2014;11(3):475-84
8. J Neurol Neurosurg Psychiatry. 2014;85(9):1003-8
9. Brain Stimul. 2012;5(4):653-5
10. Fed Reg. 1977 May 23;42(99):26318-32