User login
A distinguished 14-year editorship
In 1968, Richard S. Irwin, MD, Master FCCP, graduated from Tufts University School of Medicine. After completing medical residency training at the Tufts-New England Medical Center and pulmonary training at Columbia Presbyterian Medical Center, he has been practicing in pulmonary and critical care medicine for the last 50 years.
It was in 1979 that he became a CHEST member; in 2003-2004, he served as President of CHEST; and he has been actively involved as a CHEST leader throughout his career, serving on every major CHEST committee. But Dr. Irwin’s most beloved position has been as Editor in Chief of the journal CHEST®, a journey that began in 2005 – a position that he has filled for 14 years and that which he has recently stepped down from in June 2019. What better description of those 14 years at the helm of one of the most recognized and respected journals in chest medicine than to hear it straight from the Editor in Chief himself. In the June 2019 issue of the journal CHEST®, Dr. Irwin shares his thoughts in this Commentary: “On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.” Don’t miss it!
In 1968, Richard S. Irwin, MD, Master FCCP, graduated from Tufts University School of Medicine. After completing medical residency training at the Tufts-New England Medical Center and pulmonary training at Columbia Presbyterian Medical Center, he has been practicing in pulmonary and critical care medicine for the last 50 years.
It was in 1979 that he became a CHEST member; in 2003-2004, he served as President of CHEST; and he has been actively involved as a CHEST leader throughout his career, serving on every major CHEST committee. But Dr. Irwin’s most beloved position has been as Editor in Chief of the journal CHEST®, a journey that began in 2005 – a position that he has filled for 14 years and that which he has recently stepped down from in June 2019. What better description of those 14 years at the helm of one of the most recognized and respected journals in chest medicine than to hear it straight from the Editor in Chief himself. In the June 2019 issue of the journal CHEST®, Dr. Irwin shares his thoughts in this Commentary: “On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.” Don’t miss it!
In 1968, Richard S. Irwin, MD, Master FCCP, graduated from Tufts University School of Medicine. After completing medical residency training at the Tufts-New England Medical Center and pulmonary training at Columbia Presbyterian Medical Center, he has been practicing in pulmonary and critical care medicine for the last 50 years.
It was in 1979 that he became a CHEST member; in 2003-2004, he served as President of CHEST; and he has been actively involved as a CHEST leader throughout his career, serving on every major CHEST committee. But Dr. Irwin’s most beloved position has been as Editor in Chief of the journal CHEST®, a journey that began in 2005 – a position that he has filled for 14 years and that which he has recently stepped down from in June 2019. What better description of those 14 years at the helm of one of the most recognized and respected journals in chest medicine than to hear it straight from the Editor in Chief himself. In the June 2019 issue of the journal CHEST®, Dr. Irwin shares his thoughts in this Commentary: “On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.” Don’t miss it!
Ibrutinib tops chlorambucil against CLL
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
REPORTING FROM EHA CONGRESS
C-reactive protein testing reduced antibiotic prescribing in patients with COPD exacerbation
, according to a recent randomized, controlled trial.
Point-of-care C-reactive protein (CRP) testing led to fewer antibiotic prescriptions at the initial consultation, according to investigators participating in the PACE study, a multicenter, open-label trial of more than 600 patients with COPD enrolled at one of 86 general practices in the United Kingdom.
Patient-reported antibiotic use over the next 4 weeks was more than 20 percentage points lower for the group managed with the point-of-care strategy, compared with those who received usual care, according to the investigators, led by Christopher C. Butler, FMedSci, of the Nuffield Department of Primary Care Health Sciences at the University of Oxford (England).
Less antibiotic use and fewer prescriptions did not compromise patient-reported, disease-specific quality of life, added Dr. Butler and colleagues. Their report appears in the New England Journal of Medicine.
In the United States and in Europe, more than 80% of COPD patients with acute exacerbations will receive an antibiotic prescription, according to Dr. Butler and coauthors.
“Although many patients who have acute exacerbations of COPD are helped by these treatments, others are not,” wrote the investigators, noting that in one hospital-based study, about one in five such exacerbations were thought to be due to noninfectious causes.
The present study included patients at least 40 years of age who presented to a primary care practice with an acute exacerbation and at least one of the three Anthonisen criteria (increased dyspnea, sputum production, and sputum purulence) intended to guide antibiotic therapy in COPD. A total of 325 were randomly assigned to the CRP testing group, and 324 to a group that received just usual care.
Antibiotic use was reported by fewer patients in the CRP testing group, compared with the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31, 95% confidence interval, 0.20-0.47), the investigators reported.
Only 47.7% of patients in the CRP-guided group received antibiotic prescriptions at the initial consultation, vs. 69.7% of patients in the usual care group.
Hospitalizations over 6 months of follow-up were reported for 8.6% and 9.3% of patients in the CRP-guided and usual-care groups, respectively, while diagnoses of pneumonia were recorded for 3.0% and 4.0%. There was no clinically important difference between groups in the rate of antibiotic-related adverse effects.
“The evidence from our trial suggests that CRP-guided antibiotic prescribing for COPD exacerbations in primary care clinics may reduce patient-reported use of antibiotics and the prescribing of antibiotics by clinicians,” Dr. Butler and colleagues said in a discussion of these results.
Findings from the study by Dr. Butler and colleagues are “compelling enough” to support C-reactive protein (CRP) testing to guide antibiotic use in patient who have acute exacerbations of COPD, wrote the authors of an accompanying editorial.
“The trial achieved its objective, which was to show that CRP testing safely reduces antibiotic use,” stated Allan S. Brett, MD, and Majdi N. Al-Hasan, MB,BS, of the department of medicine at the University of South Carolina, Columbia.
Point-of-care testing of CRP could be applied even more broadly in clinical practice, Dr. Brett and Dr. Al-Hasan wrote, since testing has been shown to reduce prescribing of antibiotics for suspected lower respiratory tract infections and other common presentations in patients with no COPD.
“Whether primary care practices in the United States would embrace point-of-care CRP testing is another matter, given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement,” they noted.
Reduced antibiotic prescribing in patients with COPD likely has certain benefits, including reducing risk of Clostridioides difficile colitis, according to the authors.
By contrast, the current study did not determine which COPD patients might benefit from antibiotics, if any, nor which antibiotic might be warranted for those patients.
The study was supported by the Health Technology Assessment Program of the UK National Institute for Health Research. Dr. Butler reported disclosures related to Roche Molecular Systems and Roche Molecular Diagnostics, among others.
SOURCE: Butler CC et al. N Engl J Med. 2019 Jul 10;381:111-20. doi: 10.1056/NEJMoa1803185.
, according to a recent randomized, controlled trial.
Point-of-care C-reactive protein (CRP) testing led to fewer antibiotic prescriptions at the initial consultation, according to investigators participating in the PACE study, a multicenter, open-label trial of more than 600 patients with COPD enrolled at one of 86 general practices in the United Kingdom.
Patient-reported antibiotic use over the next 4 weeks was more than 20 percentage points lower for the group managed with the point-of-care strategy, compared with those who received usual care, according to the investigators, led by Christopher C. Butler, FMedSci, of the Nuffield Department of Primary Care Health Sciences at the University of Oxford (England).
Less antibiotic use and fewer prescriptions did not compromise patient-reported, disease-specific quality of life, added Dr. Butler and colleagues. Their report appears in the New England Journal of Medicine.
In the United States and in Europe, more than 80% of COPD patients with acute exacerbations will receive an antibiotic prescription, according to Dr. Butler and coauthors.
“Although many patients who have acute exacerbations of COPD are helped by these treatments, others are not,” wrote the investigators, noting that in one hospital-based study, about one in five such exacerbations were thought to be due to noninfectious causes.
The present study included patients at least 40 years of age who presented to a primary care practice with an acute exacerbation and at least one of the three Anthonisen criteria (increased dyspnea, sputum production, and sputum purulence) intended to guide antibiotic therapy in COPD. A total of 325 were randomly assigned to the CRP testing group, and 324 to a group that received just usual care.
Antibiotic use was reported by fewer patients in the CRP testing group, compared with the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31, 95% confidence interval, 0.20-0.47), the investigators reported.
Only 47.7% of patients in the CRP-guided group received antibiotic prescriptions at the initial consultation, vs. 69.7% of patients in the usual care group.
Hospitalizations over 6 months of follow-up were reported for 8.6% and 9.3% of patients in the CRP-guided and usual-care groups, respectively, while diagnoses of pneumonia were recorded for 3.0% and 4.0%. There was no clinically important difference between groups in the rate of antibiotic-related adverse effects.
“The evidence from our trial suggests that CRP-guided antibiotic prescribing for COPD exacerbations in primary care clinics may reduce patient-reported use of antibiotics and the prescribing of antibiotics by clinicians,” Dr. Butler and colleagues said in a discussion of these results.
Findings from the study by Dr. Butler and colleagues are “compelling enough” to support C-reactive protein (CRP) testing to guide antibiotic use in patient who have acute exacerbations of COPD, wrote the authors of an accompanying editorial.
“The trial achieved its objective, which was to show that CRP testing safely reduces antibiotic use,” stated Allan S. Brett, MD, and Majdi N. Al-Hasan, MB,BS, of the department of medicine at the University of South Carolina, Columbia.
Point-of-care testing of CRP could be applied even more broadly in clinical practice, Dr. Brett and Dr. Al-Hasan wrote, since testing has been shown to reduce prescribing of antibiotics for suspected lower respiratory tract infections and other common presentations in patients with no COPD.
“Whether primary care practices in the United States would embrace point-of-care CRP testing is another matter, given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement,” they noted.
Reduced antibiotic prescribing in patients with COPD likely has certain benefits, including reducing risk of Clostridioides difficile colitis, according to the authors.
By contrast, the current study did not determine which COPD patients might benefit from antibiotics, if any, nor which antibiotic might be warranted for those patients.
The study was supported by the Health Technology Assessment Program of the UK National Institute for Health Research. Dr. Butler reported disclosures related to Roche Molecular Systems and Roche Molecular Diagnostics, among others.
SOURCE: Butler CC et al. N Engl J Med. 2019 Jul 10;381:111-20. doi: 10.1056/NEJMoa1803185.
, according to a recent randomized, controlled trial.
Point-of-care C-reactive protein (CRP) testing led to fewer antibiotic prescriptions at the initial consultation, according to investigators participating in the PACE study, a multicenter, open-label trial of more than 600 patients with COPD enrolled at one of 86 general practices in the United Kingdom.
Patient-reported antibiotic use over the next 4 weeks was more than 20 percentage points lower for the group managed with the point-of-care strategy, compared with those who received usual care, according to the investigators, led by Christopher C. Butler, FMedSci, of the Nuffield Department of Primary Care Health Sciences at the University of Oxford (England).
Less antibiotic use and fewer prescriptions did not compromise patient-reported, disease-specific quality of life, added Dr. Butler and colleagues. Their report appears in the New England Journal of Medicine.
In the United States and in Europe, more than 80% of COPD patients with acute exacerbations will receive an antibiotic prescription, according to Dr. Butler and coauthors.
“Although many patients who have acute exacerbations of COPD are helped by these treatments, others are not,” wrote the investigators, noting that in one hospital-based study, about one in five such exacerbations were thought to be due to noninfectious causes.
The present study included patients at least 40 years of age who presented to a primary care practice with an acute exacerbation and at least one of the three Anthonisen criteria (increased dyspnea, sputum production, and sputum purulence) intended to guide antibiotic therapy in COPD. A total of 325 were randomly assigned to the CRP testing group, and 324 to a group that received just usual care.
Antibiotic use was reported by fewer patients in the CRP testing group, compared with the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31, 95% confidence interval, 0.20-0.47), the investigators reported.
Only 47.7% of patients in the CRP-guided group received antibiotic prescriptions at the initial consultation, vs. 69.7% of patients in the usual care group.
Hospitalizations over 6 months of follow-up were reported for 8.6% and 9.3% of patients in the CRP-guided and usual-care groups, respectively, while diagnoses of pneumonia were recorded for 3.0% and 4.0%. There was no clinically important difference between groups in the rate of antibiotic-related adverse effects.
“The evidence from our trial suggests that CRP-guided antibiotic prescribing for COPD exacerbations in primary care clinics may reduce patient-reported use of antibiotics and the prescribing of antibiotics by clinicians,” Dr. Butler and colleagues said in a discussion of these results.
Findings from the study by Dr. Butler and colleagues are “compelling enough” to support C-reactive protein (CRP) testing to guide antibiotic use in patient who have acute exacerbations of COPD, wrote the authors of an accompanying editorial.
“The trial achieved its objective, which was to show that CRP testing safely reduces antibiotic use,” stated Allan S. Brett, MD, and Majdi N. Al-Hasan, MB,BS, of the department of medicine at the University of South Carolina, Columbia.
Point-of-care testing of CRP could be applied even more broadly in clinical practice, Dr. Brett and Dr. Al-Hasan wrote, since testing has been shown to reduce prescribing of antibiotics for suspected lower respiratory tract infections and other common presentations in patients with no COPD.
“Whether primary care practices in the United States would embrace point-of-care CRP testing is another matter, given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement,” they noted.
Reduced antibiotic prescribing in patients with COPD likely has certain benefits, including reducing risk of Clostridioides difficile colitis, according to the authors.
By contrast, the current study did not determine which COPD patients might benefit from antibiotics, if any, nor which antibiotic might be warranted for those patients.
The study was supported by the Health Technology Assessment Program of the UK National Institute for Health Research. Dr. Butler reported disclosures related to Roche Molecular Systems and Roche Molecular Diagnostics, among others.
SOURCE: Butler CC et al. N Engl J Med. 2019 Jul 10;381:111-20. doi: 10.1056/NEJMoa1803185.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
For African Americans with MDD, more education means more benefits of friendships
A new analysis has found that, for African Americans with major depressive disorder (MDD), friendship’s mitigating benefits can vary based on education levels.
“These findings underscore the complexity of social support as a possible intervening process in depression,” wrote Ann W. Nguyen, PhD, of Case Western Reserve University in Cleveland, and her coauthors. The study was published in the Journal of Affective Disorders.
To determine how certain elements of friendship affect MDD, the researchers analyzed 3,434 responses from African Americans to the National Survey of American Life. They assessed variables such as “subjective closeness to friends,” “frequency of contact with friends,” “receipt of support from friends,” and “provision of support to friends” via responses to related questions, along with factoring in the impact of education level on 12-month MDD. Analysis was performed via logistic regression.
Among all respondents, the 12-month prevalence of MDD was 6.7%. Overall, subjective closeness and frequency of contact with friends were negatively associated with 12-month MDD. those with lower levels of education saw no association between frequency of contact and 12-month MDD. There was a similar association between receipt of support or provision of support and education: The high education group saw their probability of MDD decrease as receipt or provision of support increased.
The authors acknowledged their study’s limitations, including the impossibility of causal inferences because of its cross-sectional design. In addition, the survey only included community-dwelling adults, meaning its findings cannot be extended to institutionalized and homeless individuals. Also, each friendship variable was assessed through a single question. “Future research,” they noted, “should assess these relationship dimensions using multi-item scales, as they tend to be more stable, reliable, and precise.”
No conflicts of interest were reported.
SOURCE: Nguyen AW et al. J Affect Disord. 2019 Jun 15. doi: 10.1016/j.jad.2019.04.013
A new analysis has found that, for African Americans with major depressive disorder (MDD), friendship’s mitigating benefits can vary based on education levels.
“These findings underscore the complexity of social support as a possible intervening process in depression,” wrote Ann W. Nguyen, PhD, of Case Western Reserve University in Cleveland, and her coauthors. The study was published in the Journal of Affective Disorders.
To determine how certain elements of friendship affect MDD, the researchers analyzed 3,434 responses from African Americans to the National Survey of American Life. They assessed variables such as “subjective closeness to friends,” “frequency of contact with friends,” “receipt of support from friends,” and “provision of support to friends” via responses to related questions, along with factoring in the impact of education level on 12-month MDD. Analysis was performed via logistic regression.
Among all respondents, the 12-month prevalence of MDD was 6.7%. Overall, subjective closeness and frequency of contact with friends were negatively associated with 12-month MDD. those with lower levels of education saw no association between frequency of contact and 12-month MDD. There was a similar association between receipt of support or provision of support and education: The high education group saw their probability of MDD decrease as receipt or provision of support increased.
The authors acknowledged their study’s limitations, including the impossibility of causal inferences because of its cross-sectional design. In addition, the survey only included community-dwelling adults, meaning its findings cannot be extended to institutionalized and homeless individuals. Also, each friendship variable was assessed through a single question. “Future research,” they noted, “should assess these relationship dimensions using multi-item scales, as they tend to be more stable, reliable, and precise.”
No conflicts of interest were reported.
SOURCE: Nguyen AW et al. J Affect Disord. 2019 Jun 15. doi: 10.1016/j.jad.2019.04.013
A new analysis has found that, for African Americans with major depressive disorder (MDD), friendship’s mitigating benefits can vary based on education levels.
“These findings underscore the complexity of social support as a possible intervening process in depression,” wrote Ann W. Nguyen, PhD, of Case Western Reserve University in Cleveland, and her coauthors. The study was published in the Journal of Affective Disorders.
To determine how certain elements of friendship affect MDD, the researchers analyzed 3,434 responses from African Americans to the National Survey of American Life. They assessed variables such as “subjective closeness to friends,” “frequency of contact with friends,” “receipt of support from friends,” and “provision of support to friends” via responses to related questions, along with factoring in the impact of education level on 12-month MDD. Analysis was performed via logistic regression.
Among all respondents, the 12-month prevalence of MDD was 6.7%. Overall, subjective closeness and frequency of contact with friends were negatively associated with 12-month MDD. those with lower levels of education saw no association between frequency of contact and 12-month MDD. There was a similar association between receipt of support or provision of support and education: The high education group saw their probability of MDD decrease as receipt or provision of support increased.
The authors acknowledged their study’s limitations, including the impossibility of causal inferences because of its cross-sectional design. In addition, the survey only included community-dwelling adults, meaning its findings cannot be extended to institutionalized and homeless individuals. Also, each friendship variable was assessed through a single question. “Future research,” they noted, “should assess these relationship dimensions using multi-item scales, as they tend to be more stable, reliable, and precise.”
No conflicts of interest were reported.
SOURCE: Nguyen AW et al. J Affect Disord. 2019 Jun 15. doi: 10.1016/j.jad.2019.04.013
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Opioid exposure leads to poor perinatal and postnatal outcomes
according to data from more than 8,000 children.
Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.
A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.
The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.
Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).
The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.
The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.
“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.
The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.
Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.
Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”
Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.
“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.
The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.
Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.
SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.
according to data from more than 8,000 children.
Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.
A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.
The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.
Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).
The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.
The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.
“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.
The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.
Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.
Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”
Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.
“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.
The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.
Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.
SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.
according to data from more than 8,000 children.
Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.
A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.
The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.
Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).
The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.
The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.
“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.
The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.
Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.
Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”
Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.
“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.
The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.
Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.
SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.
FROM JAMA NETWORK OPEN
Type 2 diabetes is particularly devastating in adolescents
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
EXPERT ANALYSIS FROM ADA 2019
Psoriasis Treatment in Patients With HIV
- Nakamura M, Abrouk M, Farahnik B, et al. Psoriasis treatment in HIV-positive patients: a systematic review of systemic immunosuppressive therapies. Cutis. 2018;101:38, 42, 56.
- Patel RV, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 2: review of treatment. Cutis. 2008;82:202-210.
- Ceccarelli M, Venanzi Rullo E, Vaccaro M, et al. HIV‐associated psoriasis: epidemiology, pathogenesis, and management [published online January 6, 2019]. Dermatol Ther. 2019;32:e12806. doi:10.1111/dth.12806.
- Zarbafian M, Richer V. Treatment of moderate to severe psoriasis with apremilast over 2 years in the context of long-term treated HIV infection: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19845193. doi:10.1177/2050313X19845193.
- Menon K, Van Vorhees AS, Bebo, BF, et al. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
- Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
- Patel VA, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis. Cutis. 2008;82:117-122.
- Castillo RL, Racaza GZ, Dela Cruz Roa F. Ostraceous and inverse psoriasis with psoriatic arthritis as the presenting features of advanced HIV infection. Singapore Med J. 2014;55:e60-e63.
- Duvic M, Crane MM, Conant M, et al. Zidovudine improves psoriasis in human immunodeficiency virus- positive males. Arch Dermatol. 1994;130:447.
- Jaffee D, May LP, Sanchez M, et al. Staphylococcal sepsis in HIV antibody seropositive psoriasis patients. J Am Acad Dermatol. 1991;24:970-972.
- King LE, Dufresne RG, Lovette GL, et al. Erythroderma: review of 82 cases. South Med J. 1986;79:1210-1215.
- Kaminetsky J, Aziz M, Kaushik S. A review of biologics and other treatment modalities in HIV-associated psoriasis. Skin. 2018;2:389-401.
- Wolff K. Side effects of psoralen photochemotherapy (PUVA). Br J Dermatol. 1990;122:117-125.
- Stern RS, Mills DK, Krell K, et al. HIV-positive patients differ from HIV-negative patients in indications for and type of UV therapy used. J Am Acad Dermatol. 1998;39:48-55.
- Oracion RM, Skiest DJ, Keiser PH, et al. HIV-related skin diseases. Prog Dermatol. 1999;33:1-6.
- Finkelstein M, Berman B. HIV and AIDS in inpatient dermatology: approach to the consultation. Dermatol Clin. 2000;18:509-520.
- Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80:43-53.
- Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
- Reddy SP, Lee E, Wu JJ. Apremilast and phototherapy for treatment of psoriasis in a patient with human immunodeficiency virus. Cutis. 2019;103:E1-E7.
- Otezla (apremilast). Summit, NJ: Celgene Corporation; 2017.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
- Nakamura M, Abrouk M, Farahnik B, et al. Psoriasis treatment in HIV-positive patients: a systematic review of systemic immunosuppressive therapies. Cutis. 2018;101:38, 42, 56.
- Patel RV, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 2: review of treatment. Cutis. 2008;82:202-210.
- Ceccarelli M, Venanzi Rullo E, Vaccaro M, et al. HIV‐associated psoriasis: epidemiology, pathogenesis, and management [published online January 6, 2019]. Dermatol Ther. 2019;32:e12806. doi:10.1111/dth.12806.
- Zarbafian M, Richer V. Treatment of moderate to severe psoriasis with apremilast over 2 years in the context of long-term treated HIV infection: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19845193. doi:10.1177/2050313X19845193.
- Menon K, Van Vorhees AS, Bebo, BF, et al. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
- Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
- Patel VA, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis. Cutis. 2008;82:117-122.
- Castillo RL, Racaza GZ, Dela Cruz Roa F. Ostraceous and inverse psoriasis with psoriatic arthritis as the presenting features of advanced HIV infection. Singapore Med J. 2014;55:e60-e63.
- Duvic M, Crane MM, Conant M, et al. Zidovudine improves psoriasis in human immunodeficiency virus- positive males. Arch Dermatol. 1994;130:447.
- Jaffee D, May LP, Sanchez M, et al. Staphylococcal sepsis in HIV antibody seropositive psoriasis patients. J Am Acad Dermatol. 1991;24:970-972.
- King LE, Dufresne RG, Lovette GL, et al. Erythroderma: review of 82 cases. South Med J. 1986;79:1210-1215.
- Kaminetsky J, Aziz M, Kaushik S. A review of biologics and other treatment modalities in HIV-associated psoriasis. Skin. 2018;2:389-401.
- Wolff K. Side effects of psoralen photochemotherapy (PUVA). Br J Dermatol. 1990;122:117-125.
- Stern RS, Mills DK, Krell K, et al. HIV-positive patients differ from HIV-negative patients in indications for and type of UV therapy used. J Am Acad Dermatol. 1998;39:48-55.
- Oracion RM, Skiest DJ, Keiser PH, et al. HIV-related skin diseases. Prog Dermatol. 1999;33:1-6.
- Finkelstein M, Berman B. HIV and AIDS in inpatient dermatology: approach to the consultation. Dermatol Clin. 2000;18:509-520.
- Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80:43-53.
- Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
- Reddy SP, Lee E, Wu JJ. Apremilast and phototherapy for treatment of psoriasis in a patient with human immunodeficiency virus. Cutis. 2019;103:E1-E7.
- Otezla (apremilast). Summit, NJ: Celgene Corporation; 2017.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
- Nakamura M, Abrouk M, Farahnik B, et al. Psoriasis treatment in HIV-positive patients: a systematic review of systemic immunosuppressive therapies. Cutis. 2018;101:38, 42, 56.
- Patel RV, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 2: review of treatment. Cutis. 2008;82:202-210.
- Ceccarelli M, Venanzi Rullo E, Vaccaro M, et al. HIV‐associated psoriasis: epidemiology, pathogenesis, and management [published online January 6, 2019]. Dermatol Ther. 2019;32:e12806. doi:10.1111/dth.12806.
- Zarbafian M, Richer V. Treatment of moderate to severe psoriasis with apremilast over 2 years in the context of long-term treated HIV infection: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19845193. doi:10.1177/2050313X19845193.
- Menon K, Van Vorhees AS, Bebo, BF, et al. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
- Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
- Patel VA, Weinberg JM. Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis. Cutis. 2008;82:117-122.
- Castillo RL, Racaza GZ, Dela Cruz Roa F. Ostraceous and inverse psoriasis with psoriatic arthritis as the presenting features of advanced HIV infection. Singapore Med J. 2014;55:e60-e63.
- Duvic M, Crane MM, Conant M, et al. Zidovudine improves psoriasis in human immunodeficiency virus- positive males. Arch Dermatol. 1994;130:447.
- Jaffee D, May LP, Sanchez M, et al. Staphylococcal sepsis in HIV antibody seropositive psoriasis patients. J Am Acad Dermatol. 1991;24:970-972.
- King LE, Dufresne RG, Lovette GL, et al. Erythroderma: review of 82 cases. South Med J. 1986;79:1210-1215.
- Kaminetsky J, Aziz M, Kaushik S. A review of biologics and other treatment modalities in HIV-associated psoriasis. Skin. 2018;2:389-401.
- Wolff K. Side effects of psoralen photochemotherapy (PUVA). Br J Dermatol. 1990;122:117-125.
- Stern RS, Mills DK, Krell K, et al. HIV-positive patients differ from HIV-negative patients in indications for and type of UV therapy used. J Am Acad Dermatol. 1998;39:48-55.
- Oracion RM, Skiest DJ, Keiser PH, et al. HIV-related skin diseases. Prog Dermatol. 1999;33:1-6.
- Finkelstein M, Berman B. HIV and AIDS in inpatient dermatology: approach to the consultation. Dermatol Clin. 2000;18:509-520.
- Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80:43-53.
- Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
- Reddy SP, Lee E, Wu JJ. Apremilast and phototherapy for treatment of psoriasis in a patient with human immunodeficiency virus. Cutis. 2019;103:E1-E7.
- Otezla (apremilast). Summit, NJ: Celgene Corporation; 2017.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
R2-CHOP doesn’t improve survival in DLBCL
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
REPORTING FROM 15-ICML
Higher omega-3 fatty acid levels cut heart failure risk
Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.
Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.
To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.
The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.
A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.
The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).
An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.
The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).
The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.
“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.
Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.
The study findings suggest that revisiting omega-3 fatty acids to improve outcomes in patients with or at risk of cardiovascular disease may be worthwhile. Not only did the study predict heart failure in a range of ethnicities, but the same authors showed previously in animal models that these dietary supplements can preserve left ventricular function and reduce interstitial fibrosis.
The question is: Is it sufficient to give dietary recommendations of an increased fish consumption, or do we need to take purified pharmaceutical supplements such as those tested in trials? In other words, shall we have to go to the fish market or to the pharmacy to elevate our circulating levels of omega-3 fatty acids and, in this way, to try to prevent (or treat) HF?
The answer, at least in part, lies in additional large, randomized clinical trials that test high doses of omega-3 fatty acids along and combined with pharmacological and nonpharmacological treatments. Considering the very favorable tolerability and safety profile of this therapeutic approach, any positive results of these trials could provide us with an additional strategy to improve the outcomes of patients with HF or at high risk to develop it.
Aldo P. Maggioni, MD, of the ANMCO Research Center Heart Care Foundation, in Florence, Italy, made these remarks in an editorial. He disclosed honoraria for participation in committees of studies sponsored by Bayer, Novartis, and Fresenius.
The study findings suggest that revisiting omega-3 fatty acids to improve outcomes in patients with or at risk of cardiovascular disease may be worthwhile. Not only did the study predict heart failure in a range of ethnicities, but the same authors showed previously in animal models that these dietary supplements can preserve left ventricular function and reduce interstitial fibrosis.
The question is: Is it sufficient to give dietary recommendations of an increased fish consumption, or do we need to take purified pharmaceutical supplements such as those tested in trials? In other words, shall we have to go to the fish market or to the pharmacy to elevate our circulating levels of omega-3 fatty acids and, in this way, to try to prevent (or treat) HF?
The answer, at least in part, lies in additional large, randomized clinical trials that test high doses of omega-3 fatty acids along and combined with pharmacological and nonpharmacological treatments. Considering the very favorable tolerability and safety profile of this therapeutic approach, any positive results of these trials could provide us with an additional strategy to improve the outcomes of patients with HF or at high risk to develop it.
Aldo P. Maggioni, MD, of the ANMCO Research Center Heart Care Foundation, in Florence, Italy, made these remarks in an editorial. He disclosed honoraria for participation in committees of studies sponsored by Bayer, Novartis, and Fresenius.
The study findings suggest that revisiting omega-3 fatty acids to improve outcomes in patients with or at risk of cardiovascular disease may be worthwhile. Not only did the study predict heart failure in a range of ethnicities, but the same authors showed previously in animal models that these dietary supplements can preserve left ventricular function and reduce interstitial fibrosis.
The question is: Is it sufficient to give dietary recommendations of an increased fish consumption, or do we need to take purified pharmaceutical supplements such as those tested in trials? In other words, shall we have to go to the fish market or to the pharmacy to elevate our circulating levels of omega-3 fatty acids and, in this way, to try to prevent (or treat) HF?
The answer, at least in part, lies in additional large, randomized clinical trials that test high doses of omega-3 fatty acids along and combined with pharmacological and nonpharmacological treatments. Considering the very favorable tolerability and safety profile of this therapeutic approach, any positive results of these trials could provide us with an additional strategy to improve the outcomes of patients with HF or at high risk to develop it.
Aldo P. Maggioni, MD, of the ANMCO Research Center Heart Care Foundation, in Florence, Italy, made these remarks in an editorial. He disclosed honoraria for participation in committees of studies sponsored by Bayer, Novartis, and Fresenius.
Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.
Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.
To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.
The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.
A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.
The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).
An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.
The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).
The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.
“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.
Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.
Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.
Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.
To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.
The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.
A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.
The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).
An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.
The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).
The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.
“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.
Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.
FROM JACC
Key clinical point: Adults with high levels of eicosapentaenoic acid had significantly lower risk of heart failure than did those with lower levels of EPA.
Major finding: The percent EPA was 0.76% for individuals without heart failure vs. 0.69% for those who suffered heart failure (P = .005).
Study details: An analysis of 6,562 adults aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis.
Disclosures: Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.
Louisiana HCV program cuts costs – and hassles
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
gtwachtman@mdedge.com
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
gtwachtman@mdedge.com
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
gtwachtman@mdedge.com