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Open enrollment: Slow first week at HealthCare.gov
About 372,000 people selected a health insurance plan during the first week of Affordable Care Act open enrollment for 2019, according to the Centers for Medicare & Medicaid Services. The first week was short, with only 3 days to select coverage.
For Nov. 1-3, the exact number of plans selected was 371,676, which is about 38% less than last year’s first week, which was 4 days long, so the average number of plans selected per day was down by a little less than 18%, CMS data show.
“The final number of plan selections associated with enrollment activity during a reporting period may change due to plan modifications or cancellations,” CMS officials said, adding that the weekly data release “only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”
Open enrollment will continue for another 6 weeks, with Dec. 15 being the final day to enroll for 2019 coverage on the 39 state exchanges that use the HealthCare.gov platform.
About 372,000 people selected a health insurance plan during the first week of Affordable Care Act open enrollment for 2019, according to the Centers for Medicare & Medicaid Services. The first week was short, with only 3 days to select coverage.
For Nov. 1-3, the exact number of plans selected was 371,676, which is about 38% less than last year’s first week, which was 4 days long, so the average number of plans selected per day was down by a little less than 18%, CMS data show.
“The final number of plan selections associated with enrollment activity during a reporting period may change due to plan modifications or cancellations,” CMS officials said, adding that the weekly data release “only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”
Open enrollment will continue for another 6 weeks, with Dec. 15 being the final day to enroll for 2019 coverage on the 39 state exchanges that use the HealthCare.gov platform.
About 372,000 people selected a health insurance plan during the first week of Affordable Care Act open enrollment for 2019, according to the Centers for Medicare & Medicaid Services. The first week was short, with only 3 days to select coverage.
For Nov. 1-3, the exact number of plans selected was 371,676, which is about 38% less than last year’s first week, which was 4 days long, so the average number of plans selected per day was down by a little less than 18%, CMS data show.
“The final number of plan selections associated with enrollment activity during a reporting period may change due to plan modifications or cancellations,” CMS officials said, adding that the weekly data release “only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”
Open enrollment will continue for another 6 weeks, with Dec. 15 being the final day to enroll for 2019 coverage on the 39 state exchanges that use the HealthCare.gov platform.
New pregnancy, genetic testing guidance added to AAD’s melanoma guidelines
Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.
also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.
However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.
As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.
“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.
In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.
The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”
Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.
Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”
In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.
Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.
Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.
In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”
Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.
SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.
Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.
also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.
However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.
As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.
“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.
In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.
The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”
Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.
Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”
In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.
Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.
Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.
In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”
Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.
SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.
Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.
also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.
However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.
As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.
“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.
In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.
The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”
Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.
A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.
Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”
In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.
Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.
Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.
In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”
Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.
SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Variant not linked to CLL in Southeast Europe
DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
REPORTING FROM LEUKEMIA AND LYMPHOMA 2018
Key clinical point:
Major finding: The frequency of minor T allele was 0.107 in patients with CLL, 0.067 in patients with autoimmune hemolytic anemia, 0.036 in patients with idiopathic thrombocytopenic purpura, and 0.05 in controls.
Study details: An analysis of the frequency of the PTPN22 R620W variant in 320 individuals from the Republic of Macedonia.
Disclosures: Dr. Panovska-Stavridis did not declare any conflicts of interest.
ICYMI: Alirocumab improves cardiovascular outcomes
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Single-dose zoliflodacin successfully treats uncomplicated urogenital gonorrhea
A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.
About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.
The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.
“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.
At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.
Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.
“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.
Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.
A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.
Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.
That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.
“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.
The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.
SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.
This study represents a “step forward” in identifying new antimicrobial treatment options for patients with gonorrhea, according to Susan Blank, MD, and Demetre C. Daskalakis, MD.
“Given the challenges in clinical follow-up in this patient population, the single-dose regimen is promising,” Dr. Blank and Dr. Daskalakis wrote in a editorial.
While zoliflodacin has the potential to be an effective treatment for gonorrhea, its activity needs to be better defined, particularly in key anatomical sites of infection such as the pharynx, where limited activity was observed.
Progression of resistance of Neisseria gonorrhoeae is an “ever-present concern” given the history of the organism, the authors wrote.
“We are facing the real danger of multidrug-resistant, nearly untreatable gonorrhea,” they wrote. “To avoid untreatable cases of this high-incidence infection, we need to advance diagnostic technology and develop treatments with different mechanisms of action.”
Dr. Blank and Dr. Daskalakis are with the division of disease control in the New York City Department of Health and Mental Hygiene. Their editorial appears in the New England Journal of Medicine . Both reported having no conflicts of interest.
This study represents a “step forward” in identifying new antimicrobial treatment options for patients with gonorrhea, according to Susan Blank, MD, and Demetre C. Daskalakis, MD.
“Given the challenges in clinical follow-up in this patient population, the single-dose regimen is promising,” Dr. Blank and Dr. Daskalakis wrote in a editorial.
While zoliflodacin has the potential to be an effective treatment for gonorrhea, its activity needs to be better defined, particularly in key anatomical sites of infection such as the pharynx, where limited activity was observed.
Progression of resistance of Neisseria gonorrhoeae is an “ever-present concern” given the history of the organism, the authors wrote.
“We are facing the real danger of multidrug-resistant, nearly untreatable gonorrhea,” they wrote. “To avoid untreatable cases of this high-incidence infection, we need to advance diagnostic technology and develop treatments with different mechanisms of action.”
Dr. Blank and Dr. Daskalakis are with the division of disease control in the New York City Department of Health and Mental Hygiene. Their editorial appears in the New England Journal of Medicine . Both reported having no conflicts of interest.
This study represents a “step forward” in identifying new antimicrobial treatment options for patients with gonorrhea, according to Susan Blank, MD, and Demetre C. Daskalakis, MD.
“Given the challenges in clinical follow-up in this patient population, the single-dose regimen is promising,” Dr. Blank and Dr. Daskalakis wrote in a editorial.
While zoliflodacin has the potential to be an effective treatment for gonorrhea, its activity needs to be better defined, particularly in key anatomical sites of infection such as the pharynx, where limited activity was observed.
Progression of resistance of Neisseria gonorrhoeae is an “ever-present concern” given the history of the organism, the authors wrote.
“We are facing the real danger of multidrug-resistant, nearly untreatable gonorrhea,” they wrote. “To avoid untreatable cases of this high-incidence infection, we need to advance diagnostic technology and develop treatments with different mechanisms of action.”
Dr. Blank and Dr. Daskalakis are with the division of disease control in the New York City Department of Health and Mental Hygiene. Their editorial appears in the New England Journal of Medicine . Both reported having no conflicts of interest.
A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.
About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.
The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.
“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.
At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.
Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.
“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.
Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.
A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.
Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.
That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.
“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.
The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.
SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.
A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.
About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.
The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.
“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.
At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.
Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.
“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.
Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.
A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.
Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.
That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.
“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.
The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.
SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Cure rates of 96% and 100% were reported for urethral/cervical and rectal infections, respectively, and ranged from 50% to 82% in pharyngeal infections.
Study details: A randomized, open-label, phase 2 study including 181 patients with uncomplicated urogenital gonorrhea who received zoliflodacin or ceftriaxone.
Disclosures: The study authors reported disclosures related to AstraZeneca (parent company of Entasis Therapeutics, which is developing zoliflodacin) and other pharmaceutical companies.
Source: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.
ICYMI: Elotuzumab reduces progression risk in lenalidomide-refractory multiple myeloma
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
Patients with multiple myeloma who did not respond to treatment with lenalidomide and a proteasome inhibitor had a significantly lower risk of progression or death when receiving elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone (hazard ratio, 0.54; 95% confidence interval, 0.34-0.86; P = .008), according to results of a multicenter, randomized, open-label, phase 2 trial published in the New England Journal of Medicine 2018 Nov 7. doi: 10.1056/NEJMoa1805762.
Study results of ELOQUENT-3 were presented earlier this year at the Annual Congress of the European Hematology Association.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Can biomarkers detect concussions? It’s complicated
A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.
The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.
Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.
All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).
In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).
Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).
The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.
The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.
The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.
Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).
Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.
When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.
The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.
SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.
Concussion diagnosis has been constrained by reliance on subjective evidence, particularly in mild cases. Concussions also often result from a wide range of injuries, but focusing on sports-related concussions offers a chance to study biomarkers in a more controlled way.
These three studies represent the most comprehensive sports-related concussion biomarker work to date. The message may be that, for sports-related concussions, serum biomarkers may be able to detect the occurrence of a concussion, but they cannot predict motor, neurobehavioral, or neurocognitive outcome measures.
The study results also underline the need for larger, more complex prospective studies.
Erin Bigler, PhD, is a professor of psychology and neuroscience at Brigham Young University. Ellen Deibert, MD, is a neurologist in York, Pa. These comments were taken from an accompanying editorial (Neurology. 2018. doi: 10.1212/WNL.0000000000006609 ). Dr. Bigler and Dr. Deibert have no relevant conflicts of interest.
Concussion diagnosis has been constrained by reliance on subjective evidence, particularly in mild cases. Concussions also often result from a wide range of injuries, but focusing on sports-related concussions offers a chance to study biomarkers in a more controlled way.
These three studies represent the most comprehensive sports-related concussion biomarker work to date. The message may be that, for sports-related concussions, serum biomarkers may be able to detect the occurrence of a concussion, but they cannot predict motor, neurobehavioral, or neurocognitive outcome measures.
The study results also underline the need for larger, more complex prospective studies.
Erin Bigler, PhD, is a professor of psychology and neuroscience at Brigham Young University. Ellen Deibert, MD, is a neurologist in York, Pa. These comments were taken from an accompanying editorial (Neurology. 2018. doi: 10.1212/WNL.0000000000006609 ). Dr. Bigler and Dr. Deibert have no relevant conflicts of interest.
Concussion diagnosis has been constrained by reliance on subjective evidence, particularly in mild cases. Concussions also often result from a wide range of injuries, but focusing on sports-related concussions offers a chance to study biomarkers in a more controlled way.
These three studies represent the most comprehensive sports-related concussion biomarker work to date. The message may be that, for sports-related concussions, serum biomarkers may be able to detect the occurrence of a concussion, but they cannot predict motor, neurobehavioral, or neurocognitive outcome measures.
The study results also underline the need for larger, more complex prospective studies.
Erin Bigler, PhD, is a professor of psychology and neuroscience at Brigham Young University. Ellen Deibert, MD, is a neurologist in York, Pa. These comments were taken from an accompanying editorial (Neurology. 2018. doi: 10.1212/WNL.0000000000006609 ). Dr. Bigler and Dr. Deibert have no relevant conflicts of interest.
A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.
The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.
Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.
All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).
In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).
Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).
The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.
The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.
The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.
Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).
Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.
When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.
The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.
SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.
A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.
The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.
Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.
All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).
In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).
Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).
The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.
The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.
The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.
Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).
Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.
When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.
The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.
SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.
FROM NEUROLOGY
Key clinical point: Serum biomarkers show promise in concussion diagnosis, but much work remains.
Major finding: Serum levels of Abeta42, total tau, and S100B were elevated after concussions.
Study details: Prospective studies on 415 college athletes.
Disclosures: The study was funded by the Head Health Initiative, Banyan Biomarkers, and the United States Army Medical Research and Materiel Command.
Sources: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.
Petrous Levounis: Substance Abuse Disorders
Catch all the action at the VEITHsymposium
The VEITHsymposium, held yearly in New York City, is a world-class meeting that covers the full range of vascular surgery and treatment. Frontline Medical Communications on behalf of our publication, Vascular Specialist, will be there to cover the newest and the best in devices, drugs, and surgical treatments for arterial and venous disease and the biological systems they impact.
Check out this video and get a flavor of what we will be covering live once the meeting starts. And be sure follow our continuing coverage next week at on our website and @VascularTweets. Also, check out our in depth reporting from the meeting afterward in the upcoming pages of Vascular Specialist.
The VEITHsymposium, held yearly in New York City, is a world-class meeting that covers the full range of vascular surgery and treatment. Frontline Medical Communications on behalf of our publication, Vascular Specialist, will be there to cover the newest and the best in devices, drugs, and surgical treatments for arterial and venous disease and the biological systems they impact.
Check out this video and get a flavor of what we will be covering live once the meeting starts. And be sure follow our continuing coverage next week at on our website and @VascularTweets. Also, check out our in depth reporting from the meeting afterward in the upcoming pages of Vascular Specialist.
The VEITHsymposium, held yearly in New York City, is a world-class meeting that covers the full range of vascular surgery and treatment. Frontline Medical Communications on behalf of our publication, Vascular Specialist, will be there to cover the newest and the best in devices, drugs, and surgical treatments for arterial and venous disease and the biological systems they impact.
Check out this video and get a flavor of what we will be covering live once the meeting starts. And be sure follow our continuing coverage next week at on our website and @VascularTweets. Also, check out our in depth reporting from the meeting afterward in the upcoming pages of Vascular Specialist.
Dark-roast dementia, cocktail dermatitis, and violent good guys
Dark roast has the most
The most … best chance … dark-roast coffee may protect your brain against Parkinson’s disease, okay? Rhyming can be hard. A Canadian study recently found that the compounds in brewed coffee, called phenylindanes, may have neuroprotective effects by inhibiting amyloid-beta, tau, or alpha-synuclein. Researchers examined light roast, dark roast, and decaf dark roast and concluded that the dark roast contains stronger inhibitors. We always figured those ridiculous light-roast coffees were for the weak, but now we have proof.
Researchers also looked at the effect of caffeine. Sweet, sweet caffeine. While a potent psychoactive component, pure caffeine appeared to have no effect on amyloid-beta, tau, or alpha-synuclein aggregation. Does this mean coffee is the cure for Parkinson’s disease? Not quite yet, but keep on chuggin’. And while you’re at it, have some pomegranate, too.
Cocktail dermatitis
Dermatologist Vincent DeLeo, MD, isn’t a psychic or a seer. But he plays one in the examination room. Every now and then, a patient walks in with noninflammatory blisters or hyperpigmentation, often on their hands. Dr. DeLeo takes a look and asks if the patient was enjoying some gin and tonics the previous weekend. “They think you’re God because of course they were,” he told an audience at the recent Coastal Dermatology Symposium.
The culprit? An allergy to the dark green skin of limes, a.k.a. “margarita photodermatitis.” Dr. DeLeo says it may take a few days for the blisters to appear. And he advised colleagues to not photo test the patient because it could make things worse. As for treatment, steroids can help. So can switching to Scotch and soda.
The animals are getting high
Australian animals are getting a contact high, according to a research team that studied stream invertebrates around Melbourne. When we consume pharmaceuticals, our bodies do not totally absorb them. Now, evidence shows that the residual drugs that leave our system are ending up in waterways. What does that mean? It means animals are getting free drugs, and that’s just not fair.
The water-dwelling invertebrates are also passing on these residual compounds to other animals, like spiders who eat invertebrate larvae. Researchers also predicted that platypuses in particular might soon be exposed to high levels of antidepressants. At least the platypuses will be happy.
Health care goes to the movies
Science, as many of those involved in the time-honored but often misunderstood pursuit of truthiness would agree, is a strange, wonderful, yet fickle mistress. One day, she’ll have you comparing the quantity and quality of infant stools or shoving whooping cough bacteria up people’s noses. And the next day, she’ll invite you to join her at the local mega-movie multiplex for the latest Hollywood blockbuster.
Just ask Robert Olympia, MD, of Penn State University, Hershey, and his associates, who watched 10 superhero-based films from 2015 and 2016 and counted the violent acts committed by “good guys” and “bad guys.” Their analysis, presented at the annual meeting of the American Academy of Pediatrics in Orlando, shows that good guys committed 23 violent acts per hour, compared with 18 per hour for the bad guys. Young people who watch these movies “may be influenced by their portrayal of risk-taking behaviors and acts of violence. … Pediatric health care providers should educate families about the violence depicted in this genre of film and the potential dangers that may occur when children attempt to emulate these perceived heroes,” said Dr. Olympia.
Of course, his own superhero-ready name suggests that he may be battling – in a nonviolent way, we’re sure – Bleeding Ulcer, The Bowel Movement, Anal Fissure, Migraineur, and/or The Endoscopist in the next Avengers movie.
Dark roast has the most
The most … best chance … dark-roast coffee may protect your brain against Parkinson’s disease, okay? Rhyming can be hard. A Canadian study recently found that the compounds in brewed coffee, called phenylindanes, may have neuroprotective effects by inhibiting amyloid-beta, tau, or alpha-synuclein. Researchers examined light roast, dark roast, and decaf dark roast and concluded that the dark roast contains stronger inhibitors. We always figured those ridiculous light-roast coffees were for the weak, but now we have proof.
Researchers also looked at the effect of caffeine. Sweet, sweet caffeine. While a potent psychoactive component, pure caffeine appeared to have no effect on amyloid-beta, tau, or alpha-synuclein aggregation. Does this mean coffee is the cure for Parkinson’s disease? Not quite yet, but keep on chuggin’. And while you’re at it, have some pomegranate, too.
Cocktail dermatitis
Dermatologist Vincent DeLeo, MD, isn’t a psychic or a seer. But he plays one in the examination room. Every now and then, a patient walks in with noninflammatory blisters or hyperpigmentation, often on their hands. Dr. DeLeo takes a look and asks if the patient was enjoying some gin and tonics the previous weekend. “They think you’re God because of course they were,” he told an audience at the recent Coastal Dermatology Symposium.
The culprit? An allergy to the dark green skin of limes, a.k.a. “margarita photodermatitis.” Dr. DeLeo says it may take a few days for the blisters to appear. And he advised colleagues to not photo test the patient because it could make things worse. As for treatment, steroids can help. So can switching to Scotch and soda.
The animals are getting high
Australian animals are getting a contact high, according to a research team that studied stream invertebrates around Melbourne. When we consume pharmaceuticals, our bodies do not totally absorb them. Now, evidence shows that the residual drugs that leave our system are ending up in waterways. What does that mean? It means animals are getting free drugs, and that’s just not fair.
The water-dwelling invertebrates are also passing on these residual compounds to other animals, like spiders who eat invertebrate larvae. Researchers also predicted that platypuses in particular might soon be exposed to high levels of antidepressants. At least the platypuses will be happy.
Health care goes to the movies
Science, as many of those involved in the time-honored but often misunderstood pursuit of truthiness would agree, is a strange, wonderful, yet fickle mistress. One day, she’ll have you comparing the quantity and quality of infant stools or shoving whooping cough bacteria up people’s noses. And the next day, she’ll invite you to join her at the local mega-movie multiplex for the latest Hollywood blockbuster.
Just ask Robert Olympia, MD, of Penn State University, Hershey, and his associates, who watched 10 superhero-based films from 2015 and 2016 and counted the violent acts committed by “good guys” and “bad guys.” Their analysis, presented at the annual meeting of the American Academy of Pediatrics in Orlando, shows that good guys committed 23 violent acts per hour, compared with 18 per hour for the bad guys. Young people who watch these movies “may be influenced by their portrayal of risk-taking behaviors and acts of violence. … Pediatric health care providers should educate families about the violence depicted in this genre of film and the potential dangers that may occur when children attempt to emulate these perceived heroes,” said Dr. Olympia.
Of course, his own superhero-ready name suggests that he may be battling – in a nonviolent way, we’re sure – Bleeding Ulcer, The Bowel Movement, Anal Fissure, Migraineur, and/or The Endoscopist in the next Avengers movie.
Dark roast has the most
The most … best chance … dark-roast coffee may protect your brain against Parkinson’s disease, okay? Rhyming can be hard. A Canadian study recently found that the compounds in brewed coffee, called phenylindanes, may have neuroprotective effects by inhibiting amyloid-beta, tau, or alpha-synuclein. Researchers examined light roast, dark roast, and decaf dark roast and concluded that the dark roast contains stronger inhibitors. We always figured those ridiculous light-roast coffees were for the weak, but now we have proof.
Researchers also looked at the effect of caffeine. Sweet, sweet caffeine. While a potent psychoactive component, pure caffeine appeared to have no effect on amyloid-beta, tau, or alpha-synuclein aggregation. Does this mean coffee is the cure for Parkinson’s disease? Not quite yet, but keep on chuggin’. And while you’re at it, have some pomegranate, too.
Cocktail dermatitis
Dermatologist Vincent DeLeo, MD, isn’t a psychic or a seer. But he plays one in the examination room. Every now and then, a patient walks in with noninflammatory blisters or hyperpigmentation, often on their hands. Dr. DeLeo takes a look and asks if the patient was enjoying some gin and tonics the previous weekend. “They think you’re God because of course they were,” he told an audience at the recent Coastal Dermatology Symposium.
The culprit? An allergy to the dark green skin of limes, a.k.a. “margarita photodermatitis.” Dr. DeLeo says it may take a few days for the blisters to appear. And he advised colleagues to not photo test the patient because it could make things worse. As for treatment, steroids can help. So can switching to Scotch and soda.
The animals are getting high
Australian animals are getting a contact high, according to a research team that studied stream invertebrates around Melbourne. When we consume pharmaceuticals, our bodies do not totally absorb them. Now, evidence shows that the residual drugs that leave our system are ending up in waterways. What does that mean? It means animals are getting free drugs, and that’s just not fair.
The water-dwelling invertebrates are also passing on these residual compounds to other animals, like spiders who eat invertebrate larvae. Researchers also predicted that platypuses in particular might soon be exposed to high levels of antidepressants. At least the platypuses will be happy.
Health care goes to the movies
Science, as many of those involved in the time-honored but often misunderstood pursuit of truthiness would agree, is a strange, wonderful, yet fickle mistress. One day, she’ll have you comparing the quantity and quality of infant stools or shoving whooping cough bacteria up people’s noses. And the next day, she’ll invite you to join her at the local mega-movie multiplex for the latest Hollywood blockbuster.
Just ask Robert Olympia, MD, of Penn State University, Hershey, and his associates, who watched 10 superhero-based films from 2015 and 2016 and counted the violent acts committed by “good guys” and “bad guys.” Their analysis, presented at the annual meeting of the American Academy of Pediatrics in Orlando, shows that good guys committed 23 violent acts per hour, compared with 18 per hour for the bad guys. Young people who watch these movies “may be influenced by their portrayal of risk-taking behaviors and acts of violence. … Pediatric health care providers should educate families about the violence depicted in this genre of film and the potential dangers that may occur when children attempt to emulate these perceived heroes,” said Dr. Olympia.
Of course, his own superhero-ready name suggests that he may be battling – in a nonviolent way, we’re sure – Bleeding Ulcer, The Bowel Movement, Anal Fissure, Migraineur, and/or The Endoscopist in the next Avengers movie.