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Mortality rates higher in affiliates, compared with top-ranked hospitals
The sharing of a top-ranked cancer hospital brand across affiliate hospitals doesn’t necessarily guarantee the same quality of care, a new study suggests.
In a paper published in JAMA Network Open, researchers presented the outcomes of a cross-sectional study of 29,228 patients aged over 65 years who underwent complex cancer surgery at either 59 top-ranked hospitals or 343 affiliated hospitals.
The researchers saw a significant 40% higher 90-day mortality rate among patients who underwent complex cancer surgery at one of the affiliate hospitals, compared with those who were treated at the top-ranked hospitals (P less than .001), even after adjusting for factors such as age, comorbidity score, procedure type, and admission type.
“This is not entirely surprising, as affiliated hospitals are generally smaller, less likely to be teaching hospitals, and perform complex surgical procedures with less frequency (lower volume) when compared with top-ranked hospitals,” wrote Jessica R. Hoag, PhD, from the department of surgery at Yale University, New Haven, Conn., and her coauthors. However, including hospital characteristics in the models attenuated but did not eliminate the differences in mortality rates between top-ranked and affiliate hospitals.
The difference in 90-day mortality was particularly evident for gastrectomy, where there was a 100% higher 90-day mortality rate in affiliate hospitals, compared with top-ranked hospitals (P less than .001). The mortality rate for pancreaticoduodenectomy was 59% higher in affiliate hospitals, compared with top-ranked hospitals (P = .009); for colectomy it was 32% higher (P = .001), and for lobectomy it was 34% higher (P = .03).
The only procedure where the mortality rate was not statistically significantly different between top-ranked and affiliate hospitals was esophagectomy (odds ratio, 1.48; P = .06).
When the authors looked at standardized mortality ratios for the top-ranked and affiliate hospitals, they found that 41 of the 49 top-ranked hospitals had lower mortality ratios than their collective affiliates. In 37 cases, the difference in standardized mortality ratios between the top-ranked hospital and its affiliates was statistically significant.
Overall, 39 of the 49 top-ranked hospitals had better standardized mortality ratios than the national average, compared with 17 of the affiliated networks.
The authors wrote that their findings were important because previous studies showed affiliation status played a significant role in which hospital patients choose for their treatment.
“As a result, there is cause for concern that a proportion of the U.S. public could misinterpret brand sharing as indicating equivalent care,” they wrote, suggesting that one way to reduce mortality might therefore be to direct patients with the most risky and complex surgical requirements to top-ranked hospitals rather than affiliates, although acknowledged this might be challenging to implement.
One author reported receiving funding from the Centers for Medicare & Medicaid Services, one reported advisory board and steering committee positions with the private medical sector, and one reported receiving nonfinancial support from private industry outside the submitted work. No other conflicts of interest were reported.
SOURCE: Hoag JR et al. JAMA Netw Open. 2019 Apr 12. doi: 10.1001/jamanetworkopen.2019.1912.
Network affiliations with top-ranked hospitals could help expand access to high-quality cancer care and reduce travel times for patients who live too far away to access the top-ranked hospital itself. However, this study shows that the outcomes and quality of the flagship hospital do not necessarily translate to the affiliate hospitals in the network.
While affiliate hospitals are likely to deal with smaller numbers of complex patients and are less likely to be teaching hospitals, they do offer a way to potentially leverage their affiliation with top-ranked hospitals to improve the overall quality of care for cancer patients. The challenge is to work out how best to do this and to identify which patients are likely to do just as well at an affiliate hospital and which patients will be optimally treated at the flagship hospital.
Lesly A. Dossett, MD, MPH, is from the department of surgery at the University of Michigan, Ann Arbor. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Apr 12. doi:10.1001/jamanetworkopen.2019.1910). No conflicts of interest were reported.
Network affiliations with top-ranked hospitals could help expand access to high-quality cancer care and reduce travel times for patients who live too far away to access the top-ranked hospital itself. However, this study shows that the outcomes and quality of the flagship hospital do not necessarily translate to the affiliate hospitals in the network.
While affiliate hospitals are likely to deal with smaller numbers of complex patients and are less likely to be teaching hospitals, they do offer a way to potentially leverage their affiliation with top-ranked hospitals to improve the overall quality of care for cancer patients. The challenge is to work out how best to do this and to identify which patients are likely to do just as well at an affiliate hospital and which patients will be optimally treated at the flagship hospital.
Lesly A. Dossett, MD, MPH, is from the department of surgery at the University of Michigan, Ann Arbor. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Apr 12. doi:10.1001/jamanetworkopen.2019.1910). No conflicts of interest were reported.
Network affiliations with top-ranked hospitals could help expand access to high-quality cancer care and reduce travel times for patients who live too far away to access the top-ranked hospital itself. However, this study shows that the outcomes and quality of the flagship hospital do not necessarily translate to the affiliate hospitals in the network.
While affiliate hospitals are likely to deal with smaller numbers of complex patients and are less likely to be teaching hospitals, they do offer a way to potentially leverage their affiliation with top-ranked hospitals to improve the overall quality of care for cancer patients. The challenge is to work out how best to do this and to identify which patients are likely to do just as well at an affiliate hospital and which patients will be optimally treated at the flagship hospital.
Lesly A. Dossett, MD, MPH, is from the department of surgery at the University of Michigan, Ann Arbor. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Apr 12. doi:10.1001/jamanetworkopen.2019.1910). No conflicts of interest were reported.
The sharing of a top-ranked cancer hospital brand across affiliate hospitals doesn’t necessarily guarantee the same quality of care, a new study suggests.
In a paper published in JAMA Network Open, researchers presented the outcomes of a cross-sectional study of 29,228 patients aged over 65 years who underwent complex cancer surgery at either 59 top-ranked hospitals or 343 affiliated hospitals.
The researchers saw a significant 40% higher 90-day mortality rate among patients who underwent complex cancer surgery at one of the affiliate hospitals, compared with those who were treated at the top-ranked hospitals (P less than .001), even after adjusting for factors such as age, comorbidity score, procedure type, and admission type.
“This is not entirely surprising, as affiliated hospitals are generally smaller, less likely to be teaching hospitals, and perform complex surgical procedures with less frequency (lower volume) when compared with top-ranked hospitals,” wrote Jessica R. Hoag, PhD, from the department of surgery at Yale University, New Haven, Conn., and her coauthors. However, including hospital characteristics in the models attenuated but did not eliminate the differences in mortality rates between top-ranked and affiliate hospitals.
The difference in 90-day mortality was particularly evident for gastrectomy, where there was a 100% higher 90-day mortality rate in affiliate hospitals, compared with top-ranked hospitals (P less than .001). The mortality rate for pancreaticoduodenectomy was 59% higher in affiliate hospitals, compared with top-ranked hospitals (P = .009); for colectomy it was 32% higher (P = .001), and for lobectomy it was 34% higher (P = .03).
The only procedure where the mortality rate was not statistically significantly different between top-ranked and affiliate hospitals was esophagectomy (odds ratio, 1.48; P = .06).
When the authors looked at standardized mortality ratios for the top-ranked and affiliate hospitals, they found that 41 of the 49 top-ranked hospitals had lower mortality ratios than their collective affiliates. In 37 cases, the difference in standardized mortality ratios between the top-ranked hospital and its affiliates was statistically significant.
Overall, 39 of the 49 top-ranked hospitals had better standardized mortality ratios than the national average, compared with 17 of the affiliated networks.
The authors wrote that their findings were important because previous studies showed affiliation status played a significant role in which hospital patients choose for their treatment.
“As a result, there is cause for concern that a proportion of the U.S. public could misinterpret brand sharing as indicating equivalent care,” they wrote, suggesting that one way to reduce mortality might therefore be to direct patients with the most risky and complex surgical requirements to top-ranked hospitals rather than affiliates, although acknowledged this might be challenging to implement.
One author reported receiving funding from the Centers for Medicare & Medicaid Services, one reported advisory board and steering committee positions with the private medical sector, and one reported receiving nonfinancial support from private industry outside the submitted work. No other conflicts of interest were reported.
SOURCE: Hoag JR et al. JAMA Netw Open. 2019 Apr 12. doi: 10.1001/jamanetworkopen.2019.1912.
The sharing of a top-ranked cancer hospital brand across affiliate hospitals doesn’t necessarily guarantee the same quality of care, a new study suggests.
In a paper published in JAMA Network Open, researchers presented the outcomes of a cross-sectional study of 29,228 patients aged over 65 years who underwent complex cancer surgery at either 59 top-ranked hospitals or 343 affiliated hospitals.
The researchers saw a significant 40% higher 90-day mortality rate among patients who underwent complex cancer surgery at one of the affiliate hospitals, compared with those who were treated at the top-ranked hospitals (P less than .001), even after adjusting for factors such as age, comorbidity score, procedure type, and admission type.
“This is not entirely surprising, as affiliated hospitals are generally smaller, less likely to be teaching hospitals, and perform complex surgical procedures with less frequency (lower volume) when compared with top-ranked hospitals,” wrote Jessica R. Hoag, PhD, from the department of surgery at Yale University, New Haven, Conn., and her coauthors. However, including hospital characteristics in the models attenuated but did not eliminate the differences in mortality rates between top-ranked and affiliate hospitals.
The difference in 90-day mortality was particularly evident for gastrectomy, where there was a 100% higher 90-day mortality rate in affiliate hospitals, compared with top-ranked hospitals (P less than .001). The mortality rate for pancreaticoduodenectomy was 59% higher in affiliate hospitals, compared with top-ranked hospitals (P = .009); for colectomy it was 32% higher (P = .001), and for lobectomy it was 34% higher (P = .03).
The only procedure where the mortality rate was not statistically significantly different between top-ranked and affiliate hospitals was esophagectomy (odds ratio, 1.48; P = .06).
When the authors looked at standardized mortality ratios for the top-ranked and affiliate hospitals, they found that 41 of the 49 top-ranked hospitals had lower mortality ratios than their collective affiliates. In 37 cases, the difference in standardized mortality ratios between the top-ranked hospital and its affiliates was statistically significant.
Overall, 39 of the 49 top-ranked hospitals had better standardized mortality ratios than the national average, compared with 17 of the affiliated networks.
The authors wrote that their findings were important because previous studies showed affiliation status played a significant role in which hospital patients choose for their treatment.
“As a result, there is cause for concern that a proportion of the U.S. public could misinterpret brand sharing as indicating equivalent care,” they wrote, suggesting that one way to reduce mortality might therefore be to direct patients with the most risky and complex surgical requirements to top-ranked hospitals rather than affiliates, although acknowledged this might be challenging to implement.
One author reported receiving funding from the Centers for Medicare & Medicaid Services, one reported advisory board and steering committee positions with the private medical sector, and one reported receiving nonfinancial support from private industry outside the submitted work. No other conflicts of interest were reported.
SOURCE: Hoag JR et al. JAMA Netw Open. 2019 Apr 12. doi: 10.1001/jamanetworkopen.2019.1912.
FROM JAMA NETWORK OPEN
Four biomarkers could distinguish psoriatic arthritis from osteoarthritis
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
FROM ANNALS OF THE RHEUMATIC DISEASES
No birth rate gains from levothyroxine in pregnancy
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
FROM ENDO 2019
Key clinical point:
Major finding: Pregnancy rates and outcomes were similar in women treated with levothyroxine and those treated with placebo.
Study details: Double-blind, randomized, placebo-controlled trial in 952 women.
Disclosures: The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
Source: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Herpes zoster risk increased with some psoriasis, psoriatic arthritis treatments
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
No biological benefits from alcohol seen in rheumatoid arthritis
, according to a study published online March 20 in Arthritis Care & Research.
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his coauthors wrote that previous studies had suggested a link between moderate alcohol consumption and lower disease activity, better quality of life, and better functional status in people with rheumatoid arthritis. This link may tempt clinicians “to encourage moderate alcohol consumption among patients with RA,” the researchers wrote, and so it prompted them to examine the relationship more closely.
The researchers studied 16,762 individuals with rheumatoid arthritis in the National Databank for Rheumatic Diseases who had been asked about alcohol use and disease activity in a series of semiannual surveys, providing a total of 121,280 observations, at which 53% reported using alcohol.
Across the observations taken from the semiannual surveys, a total of 8.2% reported discontinuing alcohol consumption from one survey to the next, and 8.4% of abstainers reported initiating alcohol use. Importantly, individuals with high disease activity had a significantly shorter time to discontinuation of alcohol, and those with a moderate or high Patient Activity Scale-II (PAS-II) score were 36% more likely to stop alcohol consumption, compared with individuals who had a low PAS-II score.
Individuals who were older or obese or had more comorbidities or greater work disability were all independently more likely to discontinue alcohol use, while those less likely to give up alcohol tended to be white, male, and have higher physical and mental quality of life, higher educational level, and greater household income.
Participants with moderate or high PAS-II scores were also less likely to start consuming alcohol in comparison to those with low scores.
“Overall, these observations suggest that patients with RA are substantially less likely to use alcohol when their disease activity is high and their health and quality of life are poor,” the authors wrote. “This study also found that active drinking, recent discontinuation of drinking, and recent initiation of drinking were not associated with disease activity or death in this population when considering the reasons for the changes in behavior.”
They said this offered a different explanation for the previously observed association between alcohol use and lower disease activity by showing an effect of reverse causality rather than any biologically protective effect of alcohol.
While the study also found a strong link between discontinuation of alcohol use and increased subsequent mortality, they suggested this was also likely a function of disease activity and disability, rather than the effect of giving up alcohol.
The study was funded by grants to several authors from the Department of Veterans Affairs, the National Institutes of Health, and the Rheumatology Research Foundation. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb outside of the current work.
SOURCE: Baker J et al. Arthritis Care Res. 2019 Mar 20. doi: 10.1002/acr.23847.
, according to a study published online March 20 in Arthritis Care & Research.
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his coauthors wrote that previous studies had suggested a link between moderate alcohol consumption and lower disease activity, better quality of life, and better functional status in people with rheumatoid arthritis. This link may tempt clinicians “to encourage moderate alcohol consumption among patients with RA,” the researchers wrote, and so it prompted them to examine the relationship more closely.
The researchers studied 16,762 individuals with rheumatoid arthritis in the National Databank for Rheumatic Diseases who had been asked about alcohol use and disease activity in a series of semiannual surveys, providing a total of 121,280 observations, at which 53% reported using alcohol.
Across the observations taken from the semiannual surveys, a total of 8.2% reported discontinuing alcohol consumption from one survey to the next, and 8.4% of abstainers reported initiating alcohol use. Importantly, individuals with high disease activity had a significantly shorter time to discontinuation of alcohol, and those with a moderate or high Patient Activity Scale-II (PAS-II) score were 36% more likely to stop alcohol consumption, compared with individuals who had a low PAS-II score.
Individuals who were older or obese or had more comorbidities or greater work disability were all independently more likely to discontinue alcohol use, while those less likely to give up alcohol tended to be white, male, and have higher physical and mental quality of life, higher educational level, and greater household income.
Participants with moderate or high PAS-II scores were also less likely to start consuming alcohol in comparison to those with low scores.
“Overall, these observations suggest that patients with RA are substantially less likely to use alcohol when their disease activity is high and their health and quality of life are poor,” the authors wrote. “This study also found that active drinking, recent discontinuation of drinking, and recent initiation of drinking were not associated with disease activity or death in this population when considering the reasons for the changes in behavior.”
They said this offered a different explanation for the previously observed association between alcohol use and lower disease activity by showing an effect of reverse causality rather than any biologically protective effect of alcohol.
While the study also found a strong link between discontinuation of alcohol use and increased subsequent mortality, they suggested this was also likely a function of disease activity and disability, rather than the effect of giving up alcohol.
The study was funded by grants to several authors from the Department of Veterans Affairs, the National Institutes of Health, and the Rheumatology Research Foundation. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb outside of the current work.
SOURCE: Baker J et al. Arthritis Care Res. 2019 Mar 20. doi: 10.1002/acr.23847.
, according to a study published online March 20 in Arthritis Care & Research.
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his coauthors wrote that previous studies had suggested a link between moderate alcohol consumption and lower disease activity, better quality of life, and better functional status in people with rheumatoid arthritis. This link may tempt clinicians “to encourage moderate alcohol consumption among patients with RA,” the researchers wrote, and so it prompted them to examine the relationship more closely.
The researchers studied 16,762 individuals with rheumatoid arthritis in the National Databank for Rheumatic Diseases who had been asked about alcohol use and disease activity in a series of semiannual surveys, providing a total of 121,280 observations, at which 53% reported using alcohol.
Across the observations taken from the semiannual surveys, a total of 8.2% reported discontinuing alcohol consumption from one survey to the next, and 8.4% of abstainers reported initiating alcohol use. Importantly, individuals with high disease activity had a significantly shorter time to discontinuation of alcohol, and those with a moderate or high Patient Activity Scale-II (PAS-II) score were 36% more likely to stop alcohol consumption, compared with individuals who had a low PAS-II score.
Individuals who were older or obese or had more comorbidities or greater work disability were all independently more likely to discontinue alcohol use, while those less likely to give up alcohol tended to be white, male, and have higher physical and mental quality of life, higher educational level, and greater household income.
Participants with moderate or high PAS-II scores were also less likely to start consuming alcohol in comparison to those with low scores.
“Overall, these observations suggest that patients with RA are substantially less likely to use alcohol when their disease activity is high and their health and quality of life are poor,” the authors wrote. “This study also found that active drinking, recent discontinuation of drinking, and recent initiation of drinking were not associated with disease activity or death in this population when considering the reasons for the changes in behavior.”
They said this offered a different explanation for the previously observed association between alcohol use and lower disease activity by showing an effect of reverse causality rather than any biologically protective effect of alcohol.
While the study also found a strong link between discontinuation of alcohol use and increased subsequent mortality, they suggested this was also likely a function of disease activity and disability, rather than the effect of giving up alcohol.
The study was funded by grants to several authors from the Department of Veterans Affairs, the National Institutes of Health, and the Rheumatology Research Foundation. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb outside of the current work.
SOURCE: Baker J et al. Arthritis Care Res. 2019 Mar 20. doi: 10.1002/acr.23847.
FROM ARTHRITIS CARE & RESEARCH
Cannabis use, potency linked to psychotic disorder risk
Daily cannabis use, particularly high-potency cannabis, might be a significant contributor to the incidence of psychotic disorder, results of a multicenter, case-control study suggest.
“We provide the first direct evidence that cannabis use has an effect on variation in the incidence of psychotic disorders,” Marta Di Forti, PhD, and her coauthors wrote in the Lancet.
In the study, Dr. Di Forti and her coauthors looked at cannabis use in 901 patients presenting with a first psychotic episode to one of 11 sites across Europe and Brazil, compared with 1,237 population controls from the same locations. They found that daily cannabis users had more than threefold higher odds of psychotic disorder, compared with individuals who had never used cannabis (odds ratio, 3.2; P less than .0001), even after adjusting for sociodemographic factors and use of tobacco, stimulants, ketamine, and hallucinogenics.
Those who reported using high-potency cannabis (delta 9-tetrahydrocannabinol greater than or equal to 10%) – also showed a significant 60% increase in the odds of psychotic disorder, compared with never-users, which decreased slightly to 50% after controlling for daily use.
“The large sample size and the different types of cannabis available across Europe have allowed us to report that the dose-response relationship characterizing the association between cannabis use and psychosis reflects not only the use of high-potency cannabis but also the daily use of types with an amount of THC consistent with more traditional varieties,” wrote Dr. Di Forti, of the Social, Genetic, and Developmental Psychiatry Centre at King’s College London, and her coauthors.
When the authors looked at the population-attributable fractions, they calculated that 12.2% of cases of first-episode psychosis would be avoided if high-potency cannabis were not available.
(P = .0122), while those who started using high-potency cannabis at that age had more than a doubling of risk (OR, 2.3).
Similarly, those who used high-potency cannabis on a daily basis had nearly fivefold higher odds of psychotic disorder, compared with never-users, while daily users of low-potency had a 2.2-fold increase in risk.
Researchers also examined patterns of cannabis use and psychotic disorder across the 11 sites, which included Amsterdam, London; Cambridge, England; Madrid; Palermo, Italy; Paris; and Ribeirão Preto, Brazil.
They noted that there were significant variations in the incidence of psychotic disorder across the study sites, and that those variations correlated with the prevalence of daily cannabis use.
London and Amsterdam, where daily use was the most common, had the highest adjusted incidence rates of psychotic disorder (45.7 cases per 100,000 person-years in London and 37.9 per 100,000 person-years in Amsterdam). In contrast, the incidence in Bologna, Italy – where daily use was less frequent – was half that of London.
They estimated that 43% of new cases of psychotic disorder in Amsterdam were attributable to daily use of cannabis, and 50.3% were attributable to high-potency cannabis, compared with 1.2% and 2.3% of cases in Puy de Dôme in France.
“Use of high-potency cannabis was a strong predictor of psychotic disorder in Amsterdam, London, and Paris, where high-potency cannabis was widely available, by contrast with sites such as Palermo where this type was not yet available,” the authors wrote. “Our results show that, in areas where daily use and use of high-potency cannabis are more prevalent in the general population, there is an excess of cases of psychotic disorder.”
The authors did point out that the study relied on self-reported cannabis use, rather than biological sampling measures. But previous studies have shown self-reported use to be a reliable measure, they said.
“Education is needed to inform the public about the mental health hazards of regular use of high-potency cannabis, which is becoming increasingly available worldwide,” they wrote.
The study was supported by the Medical Research Council, the European Community’s Seventh Framework Program, the São Paulo Research Foundation, the National Institute for Health Research Biomedical Research Centre, and the Wellcome Trust. Five authors declared personal fees and grants from the pharmaceutical industry. No other conflicts of interest were declared.
SOURCE: Di Forti M et al. Lancet. 2019 Mar 19. doi: 10.1016/S2215-0366(19)30048-3.
Epidemiologic and experimental studies generally have established a link between heavy cannabis use and psychosis. However, a long-running issue has been that, while cannabis use has increased in some populations, the rates of psychosis have not necessarily done the same. The results of this study go against that, suggesting that differing rates and intensity of cannabis use across Europe appear to correlate with differing rates of psychosis.
This does not necessarily imply causality. For example, genetic studies suggest that individuals predisposed to psychosis also may have a predisposition to use cannabis. Another possibility is that subclinical mental health issues existed in those participants before the start of cannabis use. The challenge, therefore, remains to identify which individuals are most at risk from psychosis related to cannabis use, and to develop strategies aimed at mitigating this risk.
Suzanne H. Gage, PhD, is affiliated with the department of psychological sciences at the University of Liverpool in England. These comments are adapted from an accompanying editorial (Lancet. 2019 Mar 19. doi: 10.1016/ S2215-0366[19]30086-0). No conflicts of interest were declared.
Epidemiologic and experimental studies generally have established a link between heavy cannabis use and psychosis. However, a long-running issue has been that, while cannabis use has increased in some populations, the rates of psychosis have not necessarily done the same. The results of this study go against that, suggesting that differing rates and intensity of cannabis use across Europe appear to correlate with differing rates of psychosis.
This does not necessarily imply causality. For example, genetic studies suggest that individuals predisposed to psychosis also may have a predisposition to use cannabis. Another possibility is that subclinical mental health issues existed in those participants before the start of cannabis use. The challenge, therefore, remains to identify which individuals are most at risk from psychosis related to cannabis use, and to develop strategies aimed at mitigating this risk.
Suzanne H. Gage, PhD, is affiliated with the department of psychological sciences at the University of Liverpool in England. These comments are adapted from an accompanying editorial (Lancet. 2019 Mar 19. doi: 10.1016/ S2215-0366[19]30086-0). No conflicts of interest were declared.
Epidemiologic and experimental studies generally have established a link between heavy cannabis use and psychosis. However, a long-running issue has been that, while cannabis use has increased in some populations, the rates of psychosis have not necessarily done the same. The results of this study go against that, suggesting that differing rates and intensity of cannabis use across Europe appear to correlate with differing rates of psychosis.
This does not necessarily imply causality. For example, genetic studies suggest that individuals predisposed to psychosis also may have a predisposition to use cannabis. Another possibility is that subclinical mental health issues existed in those participants before the start of cannabis use. The challenge, therefore, remains to identify which individuals are most at risk from psychosis related to cannabis use, and to develop strategies aimed at mitigating this risk.
Suzanne H. Gage, PhD, is affiliated with the department of psychological sciences at the University of Liverpool in England. These comments are adapted from an accompanying editorial (Lancet. 2019 Mar 19. doi: 10.1016/ S2215-0366[19]30086-0). No conflicts of interest were declared.
Daily cannabis use, particularly high-potency cannabis, might be a significant contributor to the incidence of psychotic disorder, results of a multicenter, case-control study suggest.
“We provide the first direct evidence that cannabis use has an effect on variation in the incidence of psychotic disorders,” Marta Di Forti, PhD, and her coauthors wrote in the Lancet.
In the study, Dr. Di Forti and her coauthors looked at cannabis use in 901 patients presenting with a first psychotic episode to one of 11 sites across Europe and Brazil, compared with 1,237 population controls from the same locations. They found that daily cannabis users had more than threefold higher odds of psychotic disorder, compared with individuals who had never used cannabis (odds ratio, 3.2; P less than .0001), even after adjusting for sociodemographic factors and use of tobacco, stimulants, ketamine, and hallucinogenics.
Those who reported using high-potency cannabis (delta 9-tetrahydrocannabinol greater than or equal to 10%) – also showed a significant 60% increase in the odds of psychotic disorder, compared with never-users, which decreased slightly to 50% after controlling for daily use.
“The large sample size and the different types of cannabis available across Europe have allowed us to report that the dose-response relationship characterizing the association between cannabis use and psychosis reflects not only the use of high-potency cannabis but also the daily use of types with an amount of THC consistent with more traditional varieties,” wrote Dr. Di Forti, of the Social, Genetic, and Developmental Psychiatry Centre at King’s College London, and her coauthors.
When the authors looked at the population-attributable fractions, they calculated that 12.2% of cases of first-episode psychosis would be avoided if high-potency cannabis were not available.
(P = .0122), while those who started using high-potency cannabis at that age had more than a doubling of risk (OR, 2.3).
Similarly, those who used high-potency cannabis on a daily basis had nearly fivefold higher odds of psychotic disorder, compared with never-users, while daily users of low-potency had a 2.2-fold increase in risk.
Researchers also examined patterns of cannabis use and psychotic disorder across the 11 sites, which included Amsterdam, London; Cambridge, England; Madrid; Palermo, Italy; Paris; and Ribeirão Preto, Brazil.
They noted that there were significant variations in the incidence of psychotic disorder across the study sites, and that those variations correlated with the prevalence of daily cannabis use.
London and Amsterdam, where daily use was the most common, had the highest adjusted incidence rates of psychotic disorder (45.7 cases per 100,000 person-years in London and 37.9 per 100,000 person-years in Amsterdam). In contrast, the incidence in Bologna, Italy – where daily use was less frequent – was half that of London.
They estimated that 43% of new cases of psychotic disorder in Amsterdam were attributable to daily use of cannabis, and 50.3% were attributable to high-potency cannabis, compared with 1.2% and 2.3% of cases in Puy de Dôme in France.
“Use of high-potency cannabis was a strong predictor of psychotic disorder in Amsterdam, London, and Paris, where high-potency cannabis was widely available, by contrast with sites such as Palermo where this type was not yet available,” the authors wrote. “Our results show that, in areas where daily use and use of high-potency cannabis are more prevalent in the general population, there is an excess of cases of psychotic disorder.”
The authors did point out that the study relied on self-reported cannabis use, rather than biological sampling measures. But previous studies have shown self-reported use to be a reliable measure, they said.
“Education is needed to inform the public about the mental health hazards of regular use of high-potency cannabis, which is becoming increasingly available worldwide,” they wrote.
The study was supported by the Medical Research Council, the European Community’s Seventh Framework Program, the São Paulo Research Foundation, the National Institute for Health Research Biomedical Research Centre, and the Wellcome Trust. Five authors declared personal fees and grants from the pharmaceutical industry. No other conflicts of interest were declared.
SOURCE: Di Forti M et al. Lancet. 2019 Mar 19. doi: 10.1016/S2215-0366(19)30048-3.
Daily cannabis use, particularly high-potency cannabis, might be a significant contributor to the incidence of psychotic disorder, results of a multicenter, case-control study suggest.
“We provide the first direct evidence that cannabis use has an effect on variation in the incidence of psychotic disorders,” Marta Di Forti, PhD, and her coauthors wrote in the Lancet.
In the study, Dr. Di Forti and her coauthors looked at cannabis use in 901 patients presenting with a first psychotic episode to one of 11 sites across Europe and Brazil, compared with 1,237 population controls from the same locations. They found that daily cannabis users had more than threefold higher odds of psychotic disorder, compared with individuals who had never used cannabis (odds ratio, 3.2; P less than .0001), even after adjusting for sociodemographic factors and use of tobacco, stimulants, ketamine, and hallucinogenics.
Those who reported using high-potency cannabis (delta 9-tetrahydrocannabinol greater than or equal to 10%) – also showed a significant 60% increase in the odds of psychotic disorder, compared with never-users, which decreased slightly to 50% after controlling for daily use.
“The large sample size and the different types of cannabis available across Europe have allowed us to report that the dose-response relationship characterizing the association between cannabis use and psychosis reflects not only the use of high-potency cannabis but also the daily use of types with an amount of THC consistent with more traditional varieties,” wrote Dr. Di Forti, of the Social, Genetic, and Developmental Psychiatry Centre at King’s College London, and her coauthors.
When the authors looked at the population-attributable fractions, they calculated that 12.2% of cases of first-episode psychosis would be avoided if high-potency cannabis were not available.
(P = .0122), while those who started using high-potency cannabis at that age had more than a doubling of risk (OR, 2.3).
Similarly, those who used high-potency cannabis on a daily basis had nearly fivefold higher odds of psychotic disorder, compared with never-users, while daily users of low-potency had a 2.2-fold increase in risk.
Researchers also examined patterns of cannabis use and psychotic disorder across the 11 sites, which included Amsterdam, London; Cambridge, England; Madrid; Palermo, Italy; Paris; and Ribeirão Preto, Brazil.
They noted that there were significant variations in the incidence of psychotic disorder across the study sites, and that those variations correlated with the prevalence of daily cannabis use.
London and Amsterdam, where daily use was the most common, had the highest adjusted incidence rates of psychotic disorder (45.7 cases per 100,000 person-years in London and 37.9 per 100,000 person-years in Amsterdam). In contrast, the incidence in Bologna, Italy – where daily use was less frequent – was half that of London.
They estimated that 43% of new cases of psychotic disorder in Amsterdam were attributable to daily use of cannabis, and 50.3% were attributable to high-potency cannabis, compared with 1.2% and 2.3% of cases in Puy de Dôme in France.
“Use of high-potency cannabis was a strong predictor of psychotic disorder in Amsterdam, London, and Paris, where high-potency cannabis was widely available, by contrast with sites such as Palermo where this type was not yet available,” the authors wrote. “Our results show that, in areas where daily use and use of high-potency cannabis are more prevalent in the general population, there is an excess of cases of psychotic disorder.”
The authors did point out that the study relied on self-reported cannabis use, rather than biological sampling measures. But previous studies have shown self-reported use to be a reliable measure, they said.
“Education is needed to inform the public about the mental health hazards of regular use of high-potency cannabis, which is becoming increasingly available worldwide,” they wrote.
The study was supported by the Medical Research Council, the European Community’s Seventh Framework Program, the São Paulo Research Foundation, the National Institute for Health Research Biomedical Research Centre, and the Wellcome Trust. Five authors declared personal fees and grants from the pharmaceutical industry. No other conflicts of interest were declared.
SOURCE: Di Forti M et al. Lancet. 2019 Mar 19. doi: 10.1016/S2215-0366(19)30048-3.
FROM THE LANCET
Immediate angiography after non-STEMI cardiac arrest confers no survival benefit
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
FROM ACC 19
Antibiotic-eluting envelope reduces CIED infections
An absorbable, antibiotic-eluting envelope around cardiac implantable electronic devices could significantly reduce the incidence of infection, according to a presentation at the annual meeting of the American College of Cardiology.
The WRAP-IT trial, which was simultaneously published online March 17 in the New England Journal of Medicine, involved 6,983 patients undergoing cardiac implantable electronic device (CIED) implantation, replacement, revision, or upgrade. Patients were randomized either to receive the TYRX Absorbable Antibacterial Envelope or not.
After a mean follow-up of 20.7 months, there was a significant 40% lower rate of major infections in the envelope group compared to the control group, which met the efficacy objective of the study. Researchers saw 30 major infections in 25 patients in the envelope group; in the control group, there were 45 major infections in 42 patients (P = 0.04). The trial excluded patients at high risk of systemic infection due to other sources and patients with existing infection.
“CIED infection is a rare but serious event, and its management requires prolonged hospitalization, which involves device and lead extraction with adjunctive antibiotic therapy,” wrote Dr. Khaldoun G. Tarakji, from The Cleveland Clinic, and co-authors. “Despite proper management of CIED infection, both short- and long-term mortality remains high.”
One previous randomized study had shown that intravenous administration of antibiotics during CIED procedures can reduce the risk of infection, while a different study failed to find a benefit. The vast majority of patients in this study (98.7%) received periprocedural antibiotics, 74.5% received pocket wash and 29.6% received post-procedural antibiotics. These strategies were not controlled, but there is no clear evidence that any particular strategy influenced the infection rate, the authors wrote.
Patients in the envelope group experienced numerically fewer pocket infections but more endocarditis or bacteremia compared to those in the control group, a finding that the authors could not explain.
The most common pathogen responsible was staphylococcus, but data on antibiotic susceptibility was not collected. The authors stressed that this limited their ability to assess the risk of antibiotic resistance developing.
In this study, the researchers noted that the reduction in the risk of infection was greater among individuals who were implanted with higher-power devices, compared to those implanted with low-power devices or an initial cardiac resynchronization therapy device.
However, they said, the rate of infections was generally lower among those receiving low-power devices.
There was no increase in complications related to use of the envelope. The rate of complications occurring within 12 months of the procedure and relating to the CIED procedure or envelope was 6% in the envelope group and 6.9% in the control group.
When major infections were excluded, the rate of complications in each group was 5.7% and 5/9% respectively. There was also no significant difference in mortality rates between the two groups (17.4% and 17.8% respectively).
The authors wrote that while use of the envelope can require a slightly larger CIED dissection pocket, this was not associated with increased procedural time or complications. The envelope was successfully implanted in 99.7% of procedure attempts.
“There were fewer system revisions in the envelope group than in the control group and no complications due to allergy to the envelope mesh, polymer, or antibiotics,” they wrote.
The study was supported by Medtronic, the maker of the TYRX Absorbable Antibacterial Envelope. Twenty-four authors declared institutional funding or research grants from Medtronic, thirteen declared fees, consultancies and other support from private industry outside the submitted work. Three authors were employees of Medtronic.
SOURCE: Tarakji K et al. NEJM, 2019, March 17. DOI: 10.1056/NEJMoa1901111
An absorbable, antibiotic-eluting envelope around cardiac implantable electronic devices could significantly reduce the incidence of infection, according to a presentation at the annual meeting of the American College of Cardiology.
The WRAP-IT trial, which was simultaneously published online March 17 in the New England Journal of Medicine, involved 6,983 patients undergoing cardiac implantable electronic device (CIED) implantation, replacement, revision, or upgrade. Patients were randomized either to receive the TYRX Absorbable Antibacterial Envelope or not.
After a mean follow-up of 20.7 months, there was a significant 40% lower rate of major infections in the envelope group compared to the control group, which met the efficacy objective of the study. Researchers saw 30 major infections in 25 patients in the envelope group; in the control group, there were 45 major infections in 42 patients (P = 0.04). The trial excluded patients at high risk of systemic infection due to other sources and patients with existing infection.
“CIED infection is a rare but serious event, and its management requires prolonged hospitalization, which involves device and lead extraction with adjunctive antibiotic therapy,” wrote Dr. Khaldoun G. Tarakji, from The Cleveland Clinic, and co-authors. “Despite proper management of CIED infection, both short- and long-term mortality remains high.”
One previous randomized study had shown that intravenous administration of antibiotics during CIED procedures can reduce the risk of infection, while a different study failed to find a benefit. The vast majority of patients in this study (98.7%) received periprocedural antibiotics, 74.5% received pocket wash and 29.6% received post-procedural antibiotics. These strategies were not controlled, but there is no clear evidence that any particular strategy influenced the infection rate, the authors wrote.
Patients in the envelope group experienced numerically fewer pocket infections but more endocarditis or bacteremia compared to those in the control group, a finding that the authors could not explain.
The most common pathogen responsible was staphylococcus, but data on antibiotic susceptibility was not collected. The authors stressed that this limited their ability to assess the risk of antibiotic resistance developing.
In this study, the researchers noted that the reduction in the risk of infection was greater among individuals who were implanted with higher-power devices, compared to those implanted with low-power devices or an initial cardiac resynchronization therapy device.
However, they said, the rate of infections was generally lower among those receiving low-power devices.
There was no increase in complications related to use of the envelope. The rate of complications occurring within 12 months of the procedure and relating to the CIED procedure or envelope was 6% in the envelope group and 6.9% in the control group.
When major infections were excluded, the rate of complications in each group was 5.7% and 5/9% respectively. There was also no significant difference in mortality rates between the two groups (17.4% and 17.8% respectively).
The authors wrote that while use of the envelope can require a slightly larger CIED dissection pocket, this was not associated with increased procedural time or complications. The envelope was successfully implanted in 99.7% of procedure attempts.
“There were fewer system revisions in the envelope group than in the control group and no complications due to allergy to the envelope mesh, polymer, or antibiotics,” they wrote.
The study was supported by Medtronic, the maker of the TYRX Absorbable Antibacterial Envelope. Twenty-four authors declared institutional funding or research grants from Medtronic, thirteen declared fees, consultancies and other support from private industry outside the submitted work. Three authors were employees of Medtronic.
SOURCE: Tarakji K et al. NEJM, 2019, March 17. DOI: 10.1056/NEJMoa1901111
An absorbable, antibiotic-eluting envelope around cardiac implantable electronic devices could significantly reduce the incidence of infection, according to a presentation at the annual meeting of the American College of Cardiology.
The WRAP-IT trial, which was simultaneously published online March 17 in the New England Journal of Medicine, involved 6,983 patients undergoing cardiac implantable electronic device (CIED) implantation, replacement, revision, or upgrade. Patients were randomized either to receive the TYRX Absorbable Antibacterial Envelope or not.
After a mean follow-up of 20.7 months, there was a significant 40% lower rate of major infections in the envelope group compared to the control group, which met the efficacy objective of the study. Researchers saw 30 major infections in 25 patients in the envelope group; in the control group, there were 45 major infections in 42 patients (P = 0.04). The trial excluded patients at high risk of systemic infection due to other sources and patients with existing infection.
“CIED infection is a rare but serious event, and its management requires prolonged hospitalization, which involves device and lead extraction with adjunctive antibiotic therapy,” wrote Dr. Khaldoun G. Tarakji, from The Cleveland Clinic, and co-authors. “Despite proper management of CIED infection, both short- and long-term mortality remains high.”
One previous randomized study had shown that intravenous administration of antibiotics during CIED procedures can reduce the risk of infection, while a different study failed to find a benefit. The vast majority of patients in this study (98.7%) received periprocedural antibiotics, 74.5% received pocket wash and 29.6% received post-procedural antibiotics. These strategies were not controlled, but there is no clear evidence that any particular strategy influenced the infection rate, the authors wrote.
Patients in the envelope group experienced numerically fewer pocket infections but more endocarditis or bacteremia compared to those in the control group, a finding that the authors could not explain.
The most common pathogen responsible was staphylococcus, but data on antibiotic susceptibility was not collected. The authors stressed that this limited their ability to assess the risk of antibiotic resistance developing.
In this study, the researchers noted that the reduction in the risk of infection was greater among individuals who were implanted with higher-power devices, compared to those implanted with low-power devices or an initial cardiac resynchronization therapy device.
However, they said, the rate of infections was generally lower among those receiving low-power devices.
There was no increase in complications related to use of the envelope. The rate of complications occurring within 12 months of the procedure and relating to the CIED procedure or envelope was 6% in the envelope group and 6.9% in the control group.
When major infections were excluded, the rate of complications in each group was 5.7% and 5/9% respectively. There was also no significant difference in mortality rates between the two groups (17.4% and 17.8% respectively).
The authors wrote that while use of the envelope can require a slightly larger CIED dissection pocket, this was not associated with increased procedural time or complications. The envelope was successfully implanted in 99.7% of procedure attempts.
“There were fewer system revisions in the envelope group than in the control group and no complications due to allergy to the envelope mesh, polymer, or antibiotics,” they wrote.
The study was supported by Medtronic, the maker of the TYRX Absorbable Antibacterial Envelope. Twenty-four authors declared institutional funding or research grants from Medtronic, thirteen declared fees, consultancies and other support from private industry outside the submitted work. Three authors were employees of Medtronic.
SOURCE: Tarakji K et al. NEJM, 2019, March 17. DOI: 10.1056/NEJMoa1901111
FROM ACC 19
Light physical activity lowers CVD risk in older women
Even light physical activity can significantly reduce the risks of acquiring coronary heart disease specifically and the broad range of cardiovascular diseases in older women, new data suggests.
A paper published in JAMA Network Open reported the outcome of a prospective cohort study in 5,861 women, with a mean age of 78.5 years, who wore accelerometers for 7 days to measure physical activity.
than those in the lowest quartile of activity, who engaged in less than 3.9 hours per day, after adjusting for factors such as comorbidities, lifestyle, and cardiovascular risk.
Similarly, those in the highest quartile had an 18% lower risk of cardiovascular disease than those in the lowest quartile, after adjusting for potential confounders.
Researchers saw a significant dose-dependent decrease in the risk for incident coronary heart disease and cardiovascular disease with increasing light physical activity, such that each 1-hour increment of activity was associated with a 20% decrease in coronary heart disease risk and 10% decrease in cardiovascular disease risk.
Andrea Z. LaCroix, PhD, from the University of California, San Diego, and her coauthors noted that physical activity guidelines for aerobic activity suggest 75 minutes of vigorous physical activity or 150 minutes of moderate activity each day, but only around 25% of U.S. women aged over 75 years are estimated to meet this requirement.
“These guidelines may have discouraged PA [physical activity] when perceived to be unattainable by large segments of the population,” they wrote.
While the majority of active time in older adults is spent doing light physical activity, little is known about the cardiovascular effects of participating in this level of activity. “A major barrier has been that self-reported questionnaires measuring leisure-time PA do not adequately capture light PA that is acquired throughout the day in activities of daily living,” they wrote.
The study also looked at the impact of moderate to vigorous physical activity, finding a significant 46% reduction between the highest to lowest quartiles of activity in coronary heart disease risk and a 31% reduction in cardiovascular disease risk.
Even after adjusting for the use of lipid-lowering medication, antihypertensive medication or healthy eating scores, the results remained unchanged. The researchers also saw no change when women with angina and heart failure at baseline were excluded or when they excluded cardiovascular events that occurred during the first 6 months of follow-up.
The study was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. Six authors reported receiving funding from the study supporters and other research institutions, and one reported membership on the advisory committee for physical activity guidelines. No other conflicts of interest were reported.
SOURCE: LaCroix AZ et al. JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0419.
Older women do not get enough physical activity, so this finding that light physical activity is associated with improved coronary heart disease and cardiovascular disease outcomes supports the recent scientific report by the 2018 Physical Activity Guidelines Advisory Committee. It is also helpful in extending the evidence about the benefits of physical activity in reducing incident coronary heart disease to older women, as previous studies on this topic showed such benefits in men.
These findings should remind health care professionals, systems, and agencies to promote the 2018 Physical Activity Guidelines for Americans to all patients. Otherwise, the future health and well-being of older women is likely to suffer from the consequences of sedentary behavior and inadequate physical activity.
Gregory W. Heath, DHSc, MPH, is from the department of health and human performance at the University of Tennessee, Chattanooga. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0405). No conflicts of interest were reported.
Older women do not get enough physical activity, so this finding that light physical activity is associated with improved coronary heart disease and cardiovascular disease outcomes supports the recent scientific report by the 2018 Physical Activity Guidelines Advisory Committee. It is also helpful in extending the evidence about the benefits of physical activity in reducing incident coronary heart disease to older women, as previous studies on this topic showed such benefits in men.
These findings should remind health care professionals, systems, and agencies to promote the 2018 Physical Activity Guidelines for Americans to all patients. Otherwise, the future health and well-being of older women is likely to suffer from the consequences of sedentary behavior and inadequate physical activity.
Gregory W. Heath, DHSc, MPH, is from the department of health and human performance at the University of Tennessee, Chattanooga. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0405). No conflicts of interest were reported.
Older women do not get enough physical activity, so this finding that light physical activity is associated with improved coronary heart disease and cardiovascular disease outcomes supports the recent scientific report by the 2018 Physical Activity Guidelines Advisory Committee. It is also helpful in extending the evidence about the benefits of physical activity in reducing incident coronary heart disease to older women, as previous studies on this topic showed such benefits in men.
These findings should remind health care professionals, systems, and agencies to promote the 2018 Physical Activity Guidelines for Americans to all patients. Otherwise, the future health and well-being of older women is likely to suffer from the consequences of sedentary behavior and inadequate physical activity.
Gregory W. Heath, DHSc, MPH, is from the department of health and human performance at the University of Tennessee, Chattanooga. These comments are adapted from an accompanying editorial (JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0405). No conflicts of interest were reported.
Even light physical activity can significantly reduce the risks of acquiring coronary heart disease specifically and the broad range of cardiovascular diseases in older women, new data suggests.
A paper published in JAMA Network Open reported the outcome of a prospective cohort study in 5,861 women, with a mean age of 78.5 years, who wore accelerometers for 7 days to measure physical activity.
than those in the lowest quartile of activity, who engaged in less than 3.9 hours per day, after adjusting for factors such as comorbidities, lifestyle, and cardiovascular risk.
Similarly, those in the highest quartile had an 18% lower risk of cardiovascular disease than those in the lowest quartile, after adjusting for potential confounders.
Researchers saw a significant dose-dependent decrease in the risk for incident coronary heart disease and cardiovascular disease with increasing light physical activity, such that each 1-hour increment of activity was associated with a 20% decrease in coronary heart disease risk and 10% decrease in cardiovascular disease risk.
Andrea Z. LaCroix, PhD, from the University of California, San Diego, and her coauthors noted that physical activity guidelines for aerobic activity suggest 75 minutes of vigorous physical activity or 150 minutes of moderate activity each day, but only around 25% of U.S. women aged over 75 years are estimated to meet this requirement.
“These guidelines may have discouraged PA [physical activity] when perceived to be unattainable by large segments of the population,” they wrote.
While the majority of active time in older adults is spent doing light physical activity, little is known about the cardiovascular effects of participating in this level of activity. “A major barrier has been that self-reported questionnaires measuring leisure-time PA do not adequately capture light PA that is acquired throughout the day in activities of daily living,” they wrote.
The study also looked at the impact of moderate to vigorous physical activity, finding a significant 46% reduction between the highest to lowest quartiles of activity in coronary heart disease risk and a 31% reduction in cardiovascular disease risk.
Even after adjusting for the use of lipid-lowering medication, antihypertensive medication or healthy eating scores, the results remained unchanged. The researchers also saw no change when women with angina and heart failure at baseline were excluded or when they excluded cardiovascular events that occurred during the first 6 months of follow-up.
The study was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. Six authors reported receiving funding from the study supporters and other research institutions, and one reported membership on the advisory committee for physical activity guidelines. No other conflicts of interest were reported.
SOURCE: LaCroix AZ et al. JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0419.
Even light physical activity can significantly reduce the risks of acquiring coronary heart disease specifically and the broad range of cardiovascular diseases in older women, new data suggests.
A paper published in JAMA Network Open reported the outcome of a prospective cohort study in 5,861 women, with a mean age of 78.5 years, who wore accelerometers for 7 days to measure physical activity.
than those in the lowest quartile of activity, who engaged in less than 3.9 hours per day, after adjusting for factors such as comorbidities, lifestyle, and cardiovascular risk.
Similarly, those in the highest quartile had an 18% lower risk of cardiovascular disease than those in the lowest quartile, after adjusting for potential confounders.
Researchers saw a significant dose-dependent decrease in the risk for incident coronary heart disease and cardiovascular disease with increasing light physical activity, such that each 1-hour increment of activity was associated with a 20% decrease in coronary heart disease risk and 10% decrease in cardiovascular disease risk.
Andrea Z. LaCroix, PhD, from the University of California, San Diego, and her coauthors noted that physical activity guidelines for aerobic activity suggest 75 minutes of vigorous physical activity or 150 minutes of moderate activity each day, but only around 25% of U.S. women aged over 75 years are estimated to meet this requirement.
“These guidelines may have discouraged PA [physical activity] when perceived to be unattainable by large segments of the population,” they wrote.
While the majority of active time in older adults is spent doing light physical activity, little is known about the cardiovascular effects of participating in this level of activity. “A major barrier has been that self-reported questionnaires measuring leisure-time PA do not adequately capture light PA that is acquired throughout the day in activities of daily living,” they wrote.
The study also looked at the impact of moderate to vigorous physical activity, finding a significant 46% reduction between the highest to lowest quartiles of activity in coronary heart disease risk and a 31% reduction in cardiovascular disease risk.
Even after adjusting for the use of lipid-lowering medication, antihypertensive medication or healthy eating scores, the results remained unchanged. The researchers also saw no change when women with angina and heart failure at baseline were excluded or when they excluded cardiovascular events that occurred during the first 6 months of follow-up.
The study was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. Six authors reported receiving funding from the study supporters and other research institutions, and one reported membership on the advisory committee for physical activity guidelines. No other conflicts of interest were reported.
SOURCE: LaCroix AZ et al. JAMA Netw Open. 2019 Mar 15. doi: 10.1001/jamanetworkopen.2019.0419.
FROM JAMA NETWORK OPEN
Genomic sequencing sheds light on development of pediatric cancer
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
FROM SCIENCE
Key clinical point: Genome sequencing is providing valuable information on pediatric cancer development and progression.
Major finding: Many pediatric cancers have very different oncogenic drivers to adult cancers.
Study details: Review.
Disclosures: The review was funded by the National Cancer Institute. No conflicts of interest were declared.
Source: Sweet-Cordero EA et al. Science. 2019;363:1170-5.