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Obesity in women with RA greatly influences CRP levels
Obesity is associated with elevated C-reactive protein levels among women with rheumatoid arthritis, but this elevation reflects higher fat mass rather than RA disease activity, according to a report published online April 10 in Arthritis Care & Research.
The study findings suggest that C-reactive protein (CRP) results should be interpreted with caution among obese women with RA, noted Michael D. George, MD, of the division of rheumatology at the University of Pennsylvania, Philadelphia, and his associates.
To examine possible associations between body mass index and inflammatory markers in RA, the investigators performed a secondary analysis of data from 451 adult RA patients in three cross-sectional cohorts and 1,652 RA patients in the longitudinal Veterans Affairs Rheumatoid Arthritis Registry cohort. The investigators compared these findings with those of about 21,000 control subjects from the general population who were assessed in the 2007-2010 and 1971-1974 National Health and Nutrition Examination Survey programs.
Among women with RA, obesity was associated with elevated CRP independently of other measures of disease activity, including swollen joint count, tender joint count, and global scores of inflammation. A “strikingly similar association” was seen in the control population. This indicates that the high CRP values in obese women with RA “are not reflective of greater RA activity but rather are an expected phenomenon related to adiposity,” Dr. George and his associates said (Arthritis Care Res. 2017 Apr 10. doi: 10.1002/acr.23229).
In contrast, obesity in men with RA did not correlate with elevated CRP levels. In fact, underweight men with RA tended to have significantly higher CRP than that of normal-weight and obese men. “It was beyond the scope of this study to fully evaluate the complex relationship between RA disease activity, disease severity, weight loss, frailty, comorbidities, advancing age, and other factors that might contribute to higher levels of systemic inflammation in low-BMI men,” the investigators noted.
The National Institutes of Health, the Rheumatology Research Foundation, the U.S. Department of Veterans Affairs, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of General Medical Sciences supported the work. Dr. George reported having no relevant disclosures; his associates reported ties to Pfizer, Novartis, and Amgen.
Obesity is associated with elevated C-reactive protein levels among women with rheumatoid arthritis, but this elevation reflects higher fat mass rather than RA disease activity, according to a report published online April 10 in Arthritis Care & Research.
The study findings suggest that C-reactive protein (CRP) results should be interpreted with caution among obese women with RA, noted Michael D. George, MD, of the division of rheumatology at the University of Pennsylvania, Philadelphia, and his associates.
To examine possible associations between body mass index and inflammatory markers in RA, the investigators performed a secondary analysis of data from 451 adult RA patients in three cross-sectional cohorts and 1,652 RA patients in the longitudinal Veterans Affairs Rheumatoid Arthritis Registry cohort. The investigators compared these findings with those of about 21,000 control subjects from the general population who were assessed in the 2007-2010 and 1971-1974 National Health and Nutrition Examination Survey programs.
Among women with RA, obesity was associated with elevated CRP independently of other measures of disease activity, including swollen joint count, tender joint count, and global scores of inflammation. A “strikingly similar association” was seen in the control population. This indicates that the high CRP values in obese women with RA “are not reflective of greater RA activity but rather are an expected phenomenon related to adiposity,” Dr. George and his associates said (Arthritis Care Res. 2017 Apr 10. doi: 10.1002/acr.23229).
In contrast, obesity in men with RA did not correlate with elevated CRP levels. In fact, underweight men with RA tended to have significantly higher CRP than that of normal-weight and obese men. “It was beyond the scope of this study to fully evaluate the complex relationship between RA disease activity, disease severity, weight loss, frailty, comorbidities, advancing age, and other factors that might contribute to higher levels of systemic inflammation in low-BMI men,” the investigators noted.
The National Institutes of Health, the Rheumatology Research Foundation, the U.S. Department of Veterans Affairs, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of General Medical Sciences supported the work. Dr. George reported having no relevant disclosures; his associates reported ties to Pfizer, Novartis, and Amgen.
Obesity is associated with elevated C-reactive protein levels among women with rheumatoid arthritis, but this elevation reflects higher fat mass rather than RA disease activity, according to a report published online April 10 in Arthritis Care & Research.
The study findings suggest that C-reactive protein (CRP) results should be interpreted with caution among obese women with RA, noted Michael D. George, MD, of the division of rheumatology at the University of Pennsylvania, Philadelphia, and his associates.
To examine possible associations between body mass index and inflammatory markers in RA, the investigators performed a secondary analysis of data from 451 adult RA patients in three cross-sectional cohorts and 1,652 RA patients in the longitudinal Veterans Affairs Rheumatoid Arthritis Registry cohort. The investigators compared these findings with those of about 21,000 control subjects from the general population who were assessed in the 2007-2010 and 1971-1974 National Health and Nutrition Examination Survey programs.
Among women with RA, obesity was associated with elevated CRP independently of other measures of disease activity, including swollen joint count, tender joint count, and global scores of inflammation. A “strikingly similar association” was seen in the control population. This indicates that the high CRP values in obese women with RA “are not reflective of greater RA activity but rather are an expected phenomenon related to adiposity,” Dr. George and his associates said (Arthritis Care Res. 2017 Apr 10. doi: 10.1002/acr.23229).
In contrast, obesity in men with RA did not correlate with elevated CRP levels. In fact, underweight men with RA tended to have significantly higher CRP than that of normal-weight and obese men. “It was beyond the scope of this study to fully evaluate the complex relationship between RA disease activity, disease severity, weight loss, frailty, comorbidities, advancing age, and other factors that might contribute to higher levels of systemic inflammation in low-BMI men,” the investigators noted.
The National Institutes of Health, the Rheumatology Research Foundation, the U.S. Department of Veterans Affairs, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of General Medical Sciences supported the work. Dr. George reported having no relevant disclosures; his associates reported ties to Pfizer, Novartis, and Amgen.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Among women with RA, obesity was associated with elevated CRP independently of other measures of disease activity, including swollen joint count, tender joint count, and global scores of inflammation.
Data source: A secondary analysis of data from cross-sectional and longitudinal cohort studies involving 2,103 adults with RA.
Disclosures: The National Institutes of Health, the Rheumatology Research Foundation, the U.S. Department of Veterans Affairs, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of General Medical Sciences supported the work. Dr. George reported having no relevant disclosures; his associates reported ties to Pfizer, Novartis, and Amgen.
PAP sensor may cut real-world heart failure hospitalization
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
FROM ACC 17
Key clinical point: Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant reduction in HF hospitalizations and associated substantial costs.
Major finding: The cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55).
Data source: A retrospective observational cohort study comparing HF hospitalizations during the 6 months before and the 6 months after PAP sensor implantation in 1,114 Medicare patients.
Disclosures: The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Weight fluctuations linked to higher mortality, CV events
Weight fluctuations – like the typical pattern of weight loss followed by partial or total regain that affects most people attempting to lose weight – are strongly associated with higher mortality, more cardiovascular events, and new-onset diabetes, according to an analysis of the Treating to New Targets trial published online April 6 in the New England Journal of Medicine.
Weight loss is commonly prescribed as a lifestyle intervention to improve health, especially cardiovascular health. However, “the usual pattern for most patients ... is weight loss followed by weight gain” (also termed weight cycling), which has been linked to poor cardiovascular outcomes, especially when the pattern is repeated over time, said Sripal Bangalore, MD, of New York University, and his coinvestigators.
The primary outcome measure – the composite rate of death from coronary heart disease, nonfatal MI, resuscitated cardiac arrest, revascularization, or angina – was significantly associated with weight fluctuations in a dose-dependent fashion so that greater degrees of variability in body weight were linked to higher event rates (N Engl J Med. 2017 April 6. doi: 10.1056/NEJMoa1606148).
“When compared with the lowest quintile, patients with the highest quintile of variability had an increase in the risk of any coronary event of 64%, an increase in the risk of any cardiovascular event of 85%, an increase in the risk of death of 124%, an increase in the risk of MI of 117%, an increase in the risk of stroke of 136%, and an increase in the risk of new-onset diabetes of 78%, independent of traditional risk factors,” Dr. Bangalore and his associates reported.
This association remained strong regardless of the patients’ weight at baseline, consistent among those of normal body weight and those who were overweight or obese. And the association also persisted across multiple sensitivity analyses.
This study was supported by Pfizer. Dr. Bangalore reported serving as a consultant to Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, Merck, Menarini, Gilead, and Abbott Vascular; his associates reported ties to numerous industry sources.
Weight fluctuations – like the typical pattern of weight loss followed by partial or total regain that affects most people attempting to lose weight – are strongly associated with higher mortality, more cardiovascular events, and new-onset diabetes, according to an analysis of the Treating to New Targets trial published online April 6 in the New England Journal of Medicine.
Weight loss is commonly prescribed as a lifestyle intervention to improve health, especially cardiovascular health. However, “the usual pattern for most patients ... is weight loss followed by weight gain” (also termed weight cycling), which has been linked to poor cardiovascular outcomes, especially when the pattern is repeated over time, said Sripal Bangalore, MD, of New York University, and his coinvestigators.
The primary outcome measure – the composite rate of death from coronary heart disease, nonfatal MI, resuscitated cardiac arrest, revascularization, or angina – was significantly associated with weight fluctuations in a dose-dependent fashion so that greater degrees of variability in body weight were linked to higher event rates (N Engl J Med. 2017 April 6. doi: 10.1056/NEJMoa1606148).
“When compared with the lowest quintile, patients with the highest quintile of variability had an increase in the risk of any coronary event of 64%, an increase in the risk of any cardiovascular event of 85%, an increase in the risk of death of 124%, an increase in the risk of MI of 117%, an increase in the risk of stroke of 136%, and an increase in the risk of new-onset diabetes of 78%, independent of traditional risk factors,” Dr. Bangalore and his associates reported.
This association remained strong regardless of the patients’ weight at baseline, consistent among those of normal body weight and those who were overweight or obese. And the association also persisted across multiple sensitivity analyses.
This study was supported by Pfizer. Dr. Bangalore reported serving as a consultant to Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, Merck, Menarini, Gilead, and Abbott Vascular; his associates reported ties to numerous industry sources.
Weight fluctuations – like the typical pattern of weight loss followed by partial or total regain that affects most people attempting to lose weight – are strongly associated with higher mortality, more cardiovascular events, and new-onset diabetes, according to an analysis of the Treating to New Targets trial published online April 6 in the New England Journal of Medicine.
Weight loss is commonly prescribed as a lifestyle intervention to improve health, especially cardiovascular health. However, “the usual pattern for most patients ... is weight loss followed by weight gain” (also termed weight cycling), which has been linked to poor cardiovascular outcomes, especially when the pattern is repeated over time, said Sripal Bangalore, MD, of New York University, and his coinvestigators.
The primary outcome measure – the composite rate of death from coronary heart disease, nonfatal MI, resuscitated cardiac arrest, revascularization, or angina – was significantly associated with weight fluctuations in a dose-dependent fashion so that greater degrees of variability in body weight were linked to higher event rates (N Engl J Med. 2017 April 6. doi: 10.1056/NEJMoa1606148).
“When compared with the lowest quintile, patients with the highest quintile of variability had an increase in the risk of any coronary event of 64%, an increase in the risk of any cardiovascular event of 85%, an increase in the risk of death of 124%, an increase in the risk of MI of 117%, an increase in the risk of stroke of 136%, and an increase in the risk of new-onset diabetes of 78%, independent of traditional risk factors,” Dr. Bangalore and his associates reported.
This association remained strong regardless of the patients’ weight at baseline, consistent among those of normal body weight and those who were overweight or obese. And the association also persisted across multiple sensitivity analyses.
This study was supported by Pfizer. Dr. Bangalore reported serving as a consultant to Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, Merck, Menarini, Gilead, and Abbott Vascular; his associates reported ties to numerous industry sources.
Key clinical point: Weight fluctuations are strongly associated with higher mortality, more cardiovascular events, and new-onset diabetes.
Major finding: Patients with the highest quintile of weight variability had increased risks of coronary events (64%), cardiovascular events (85%), death (124%), MI (117%), stroke (136%), and new-onset diabetes (78%).
Data source: A secondary analysis of data for 9,509 adults with coronary artery disease participating in the Treating to New Targets trial of cholesterol therapy.
Disclosures: This study was supported by Pfizer. Dr. Bangalore reported serving as a consultant to Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, Merck, Menarini, Gilead, and Abbott Vascular; his associates reported ties to numerous industry sources.
Stopping TNF inhibitors for pregnancy may invite flares
Women with rheumatoid arthritis or axial spondyloarthritis who stop treatment with tumor necrosis factor inhibitors when they become pregnant may be inviting disease flares during the pregnancy, according to a report published in Arthritis Research & Therapy.
To examine the frequency of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) flares during pregnancy, researchers prospectively followed 136 women treated at the Center for Pregnancy in Rheumatic Diseases at Inselspital Bern (Switzerland) during a 5-year period. These patients – 75 with RA and 61 with axSpA – were assessed before conception, during each trimester, and 6-8 weeks postpartum for disease activity and medication use, said Stephanie van den Brandt, MD, of the department of rheumatology, immunology, and allergology at the University of Bern, and her associates.
The relative risk of a disease flare was 3.33 among RA patients and 3.08 among axSpA patients who discontinued TNF inhibitors at the time of a positive pregnancy test. In comparison, rheumatic disease remained stable throughout pregnancy in most women who were not taking TNF inhibitors before pregnancy, the investigators said (Arthritis Res Ther. 2017 Mar 20. doi: 10.1186/s13075-017-1269-1).
Most disease flares occurred in the first trimester among women with RA and in the second half of pregnancy among women with axSpA. Most women with RA who resumed taking TNF inhibitors when their disease flared responded well to the treatment, with CRP levels dropping by 70% and remission being achieved rapidly. In contrast, most women with axSpA who resumed taking TNF inhibitors did not respond as well, with CRP levels dropping by only 35%. Their disease was ameliorated but not controlled by restarting the therapy.
No sponsor was cited for this study. Dr. van den Brandt and her associates reported having no relevant financial disclosures.
Women with rheumatoid arthritis or axial spondyloarthritis who stop treatment with tumor necrosis factor inhibitors when they become pregnant may be inviting disease flares during the pregnancy, according to a report published in Arthritis Research & Therapy.
To examine the frequency of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) flares during pregnancy, researchers prospectively followed 136 women treated at the Center for Pregnancy in Rheumatic Diseases at Inselspital Bern (Switzerland) during a 5-year period. These patients – 75 with RA and 61 with axSpA – were assessed before conception, during each trimester, and 6-8 weeks postpartum for disease activity and medication use, said Stephanie van den Brandt, MD, of the department of rheumatology, immunology, and allergology at the University of Bern, and her associates.
The relative risk of a disease flare was 3.33 among RA patients and 3.08 among axSpA patients who discontinued TNF inhibitors at the time of a positive pregnancy test. In comparison, rheumatic disease remained stable throughout pregnancy in most women who were not taking TNF inhibitors before pregnancy, the investigators said (Arthritis Res Ther. 2017 Mar 20. doi: 10.1186/s13075-017-1269-1).
Most disease flares occurred in the first trimester among women with RA and in the second half of pregnancy among women with axSpA. Most women with RA who resumed taking TNF inhibitors when their disease flared responded well to the treatment, with CRP levels dropping by 70% and remission being achieved rapidly. In contrast, most women with axSpA who resumed taking TNF inhibitors did not respond as well, with CRP levels dropping by only 35%. Their disease was ameliorated but not controlled by restarting the therapy.
No sponsor was cited for this study. Dr. van den Brandt and her associates reported having no relevant financial disclosures.
Women with rheumatoid arthritis or axial spondyloarthritis who stop treatment with tumor necrosis factor inhibitors when they become pregnant may be inviting disease flares during the pregnancy, according to a report published in Arthritis Research & Therapy.
To examine the frequency of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) flares during pregnancy, researchers prospectively followed 136 women treated at the Center for Pregnancy in Rheumatic Diseases at Inselspital Bern (Switzerland) during a 5-year period. These patients – 75 with RA and 61 with axSpA – were assessed before conception, during each trimester, and 6-8 weeks postpartum for disease activity and medication use, said Stephanie van den Brandt, MD, of the department of rheumatology, immunology, and allergology at the University of Bern, and her associates.
The relative risk of a disease flare was 3.33 among RA patients and 3.08 among axSpA patients who discontinued TNF inhibitors at the time of a positive pregnancy test. In comparison, rheumatic disease remained stable throughout pregnancy in most women who were not taking TNF inhibitors before pregnancy, the investigators said (Arthritis Res Ther. 2017 Mar 20. doi: 10.1186/s13075-017-1269-1).
Most disease flares occurred in the first trimester among women with RA and in the second half of pregnancy among women with axSpA. Most women with RA who resumed taking TNF inhibitors when their disease flared responded well to the treatment, with CRP levels dropping by 70% and remission being achieved rapidly. In contrast, most women with axSpA who resumed taking TNF inhibitors did not respond as well, with CRP levels dropping by only 35%. Their disease was ameliorated but not controlled by restarting the therapy.
No sponsor was cited for this study. Dr. van den Brandt and her associates reported having no relevant financial disclosures.
Key clinical point:
Major finding: The relative risk of a disease flare was 3.33 among RA patients and 3.08 among axSpA patients who discontinued TNF inhibitors at conception.
Data source: A prospective cohort study involving 75 pregnant women with RA and 61 with axial spondyloarthritis treated at one Swiss specialty center in 2000-2015.
Disclosures: No sponsor was cited for this study. Dr. van den Brandt and her associates reported having no relevant financial disclosures.
Hepatitis B, C appear to raise Parkinson’s risk
Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.
The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.
The findings presented by Dr. Pakpoor and her associates justify performing deep-sequencing studies in brain tissue samples at autopsy or in cerebrospinal fluid samples from patients with PD, to detect possible links with infectious agents such as viral hepatitis.
However, for any such link to be considered conclusive, future research also must show that direct-acting antiviral therapies for chronic HCV improve PD symptoms, or epidemiology studies must demonstrate a strong association with specific hepatitis virus.
Julian Benito-Leon, MD, PhD, is in the department of neurology at Complutense University Hospital, Madrid. He reported having no relevant financial disclosures. Dr. Benito-Leon made these remarks in an editorial accompanying Dr. Pakpoor’s report (Neurology. 2017;88:1-2).
The findings presented by Dr. Pakpoor and her associates justify performing deep-sequencing studies in brain tissue samples at autopsy or in cerebrospinal fluid samples from patients with PD, to detect possible links with infectious agents such as viral hepatitis.
However, for any such link to be considered conclusive, future research also must show that direct-acting antiviral therapies for chronic HCV improve PD symptoms, or epidemiology studies must demonstrate a strong association with specific hepatitis virus.
Julian Benito-Leon, MD, PhD, is in the department of neurology at Complutense University Hospital, Madrid. He reported having no relevant financial disclosures. Dr. Benito-Leon made these remarks in an editorial accompanying Dr. Pakpoor’s report (Neurology. 2017;88:1-2).
The findings presented by Dr. Pakpoor and her associates justify performing deep-sequencing studies in brain tissue samples at autopsy or in cerebrospinal fluid samples from patients with PD, to detect possible links with infectious agents such as viral hepatitis.
However, for any such link to be considered conclusive, future research also must show that direct-acting antiviral therapies for chronic HCV improve PD symptoms, or epidemiology studies must demonstrate a strong association with specific hepatitis virus.
Julian Benito-Leon, MD, PhD, is in the department of neurology at Complutense University Hospital, Madrid. He reported having no relevant financial disclosures. Dr. Benito-Leon made these remarks in an editorial accompanying Dr. Pakpoor’s report (Neurology. 2017;88:1-2).
Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.
The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.
Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.
The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.
FROM NEUROLOGY
Key clinical point:
Major finding: The risk of developing PD was significantly elevated for only 1 or more years following hospitalization for hepatitis B (RR, 1.76) or hepatitis C (RR, 1.51).
Data source: A retrospective cohort study involving 70,061 people in the general U.K. population with hepatitis B or C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects hospitalized during 1999-2011.
Disclosures: The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.
Levothyroxine: No benefit for subclinical hypothyroidism in elderly
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.
An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
The mean age of the study participants was 74 years, and they were followed for a median of 18 months after initiating treatment. The active intervention did boost thyroid function as expected, compared with placebo.
The two primary outcome measures were change between baseline and 1 year in hypothyroid symptoms and in tiredness scores on the 100-point ThyPRO (Thyroid-Related Quality of Life Patient-Reported Outcome) measure. There were no significant differences between the two study groups in changes in either of these scores. The mean 1-year score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo, and the mean 1-year score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Secondary outcomes also did not differ significantly between the two study groups, including general health-related quality of life; hand-grip strength (reflecting possible effects on skeletal muscle); executive cognitive function (reflecting possible effects on the brain); blood pressure, weight, body mass index, and waist circumference (reflecting possible effects on cardiovascular health); or activities of daily living. In addition, both fatal and nonfatal cardiovascular events were similar between the two study groups at 1 year and at extended 3-year follow-up.
Further analyses did not identify any subgroup of adults who benefited from active treatment. The lack of benefit extended across all older age groups, both genders, and all serum thyrotropin levels at baseline. In addition, all the sensitivity analyses confirmed the results of the main analysis.
Adverse events also were not significantly different between the two study groups. This included four serious adverse events of special interest: new-onset atrial fibrillation, heart failure, fracture, or osteoporosis. There also was no increase in symptoms of hyperthyroidism in the active-treatment group.
FROM ENDO 2017
Key clinical point: Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the therapy.
Major finding: The mean score for hypothyroid symptoms was 16.6 for levothyroxine and 16.7 for placebo after 1 year of treatment, and the mean score for tiredness was 28.7 for levothyroxine and 28.6 for placebo.
Data source: An international randomized double-blind placebo-controlled clinical trial involving 737 older patients with subclinical hypothyroidism.
Disclosures: This study was supported by the European Union and several foundations. The levothyroxine and matching placebo were provided free of charge by Merck, which played no role in the design, analysis, or reporting of the study. Dr. Stott reported having no relevant financial disclosures; one of his associates reported ties to Bristol/Myers Squibb, Pfizer, and Bayer.
Exposure to HPV vaccine in pregnancy not linked to birth defects
The quadrivalent human papillomavirus (HPV) vaccine was not associated with any adverse pregnancy outcomes when inadvertently given during pregnancy, according to the findings from a nationwide Danish study.
“Our results are consistent with other evidence that does not indicate that the vaccination of pregnant women with inactivated virus, bacterial, or toxoid vaccines generally confers a higher risk of adverse pregnancy outcomes than no such vaccination. Our results also confirm and considerably expand on results from previous studies of the quadrivalent HPV vaccine,” wrote Nikolai M. Scheller, MD, of the Statens Serum Institut, Copenhagen, and his colleagues.
Quadrivalent HPV vaccination was not associated with any increase in risk for major birth defects (prevalence odds ratio, 1.19), spontaneous abortion (hazard ratio, 0.71), preterm birth (prevalence OR, 1.15), small size for gestational age (prevalence OR, 0.86), or low birth weight (prevalence OR, 1.10). It also was not associated with increased risk for stillbirth, but this outcome occurred in only two case patients and four controls, making it “impossible to draw clinically meaningful conclusions” regarding the risk for stillbirth, Dr. Scheller and his colleagues reported (N Engl J Med. 2017;376[13]:1223-33).
“Because many [adverse] pregnancy outcomes are rare, our study did not have the statistical power to assess the risks of stillbirth and specific major birth defects associated with quadrivalent HPV vaccination. Larger studies would be needed to address these outcomes,” they added.
Novo Nordisk and the Danish Medical Research Council funded the study. Dr. Scheller reported having no relevant financial disclosures; two of his coauthors reported receiving research grants from the Novo Nordisk Foundation and the Danish Medical Research Council.
Although a large number of women (1,665) were immunized in the first trimester of pregnancy, when organogenesis occurs, their offspring did not have a significantly higher rate of major birth defects compared with offspring born to unvaccinated women. The numbers of spontaneous abortions, preterm births, infants with low birth weight, infants who were small for gestational age, and stillbirths were not higher in the vaccinated cohorts than in the unvaccinated cohorts, although the number of stillbirths was small.
These data are very encouraging and strongly support the safety of HPV vaccines if they are inadvertently given in pregnancy, a finding that complements previous safety reports of HPV vaccine in nonpregnant women. These data also show that adverse outcomes occur at a baseline rate in pregnancy and that when no control group is included in studies, these outcomes may be inappropriately attributed to the vaccine.
Kathryn M. Edwards, MD, is in the division of infectious diseases and the department of pediatrics at Vanderbilt University, Nashville, Tenn. She reported receiving grants from Novartis for research on group B strep vaccines in pregnancy. These comments are excerpted from an accompanying editorial (N Engl J Med. 2017;376[13]:1280-2).
Although a large number of women (1,665) were immunized in the first trimester of pregnancy, when organogenesis occurs, their offspring did not have a significantly higher rate of major birth defects compared with offspring born to unvaccinated women. The numbers of spontaneous abortions, preterm births, infants with low birth weight, infants who were small for gestational age, and stillbirths were not higher in the vaccinated cohorts than in the unvaccinated cohorts, although the number of stillbirths was small.
These data are very encouraging and strongly support the safety of HPV vaccines if they are inadvertently given in pregnancy, a finding that complements previous safety reports of HPV vaccine in nonpregnant women. These data also show that adverse outcomes occur at a baseline rate in pregnancy and that when no control group is included in studies, these outcomes may be inappropriately attributed to the vaccine.
Kathryn M. Edwards, MD, is in the division of infectious diseases and the department of pediatrics at Vanderbilt University, Nashville, Tenn. She reported receiving grants from Novartis for research on group B strep vaccines in pregnancy. These comments are excerpted from an accompanying editorial (N Engl J Med. 2017;376[13]:1280-2).
Although a large number of women (1,665) were immunized in the first trimester of pregnancy, when organogenesis occurs, their offspring did not have a significantly higher rate of major birth defects compared with offspring born to unvaccinated women. The numbers of spontaneous abortions, preterm births, infants with low birth weight, infants who were small for gestational age, and stillbirths were not higher in the vaccinated cohorts than in the unvaccinated cohorts, although the number of stillbirths was small.
These data are very encouraging and strongly support the safety of HPV vaccines if they are inadvertently given in pregnancy, a finding that complements previous safety reports of HPV vaccine in nonpregnant women. These data also show that adverse outcomes occur at a baseline rate in pregnancy and that when no control group is included in studies, these outcomes may be inappropriately attributed to the vaccine.
Kathryn M. Edwards, MD, is in the division of infectious diseases and the department of pediatrics at Vanderbilt University, Nashville, Tenn. She reported receiving grants from Novartis for research on group B strep vaccines in pregnancy. These comments are excerpted from an accompanying editorial (N Engl J Med. 2017;376[13]:1280-2).
The quadrivalent human papillomavirus (HPV) vaccine was not associated with any adverse pregnancy outcomes when inadvertently given during pregnancy, according to the findings from a nationwide Danish study.
“Our results are consistent with other evidence that does not indicate that the vaccination of pregnant women with inactivated virus, bacterial, or toxoid vaccines generally confers a higher risk of adverse pregnancy outcomes than no such vaccination. Our results also confirm and considerably expand on results from previous studies of the quadrivalent HPV vaccine,” wrote Nikolai M. Scheller, MD, of the Statens Serum Institut, Copenhagen, and his colleagues.
Quadrivalent HPV vaccination was not associated with any increase in risk for major birth defects (prevalence odds ratio, 1.19), spontaneous abortion (hazard ratio, 0.71), preterm birth (prevalence OR, 1.15), small size for gestational age (prevalence OR, 0.86), or low birth weight (prevalence OR, 1.10). It also was not associated with increased risk for stillbirth, but this outcome occurred in only two case patients and four controls, making it “impossible to draw clinically meaningful conclusions” regarding the risk for stillbirth, Dr. Scheller and his colleagues reported (N Engl J Med. 2017;376[13]:1223-33).
“Because many [adverse] pregnancy outcomes are rare, our study did not have the statistical power to assess the risks of stillbirth and specific major birth defects associated with quadrivalent HPV vaccination. Larger studies would be needed to address these outcomes,” they added.
Novo Nordisk and the Danish Medical Research Council funded the study. Dr. Scheller reported having no relevant financial disclosures; two of his coauthors reported receiving research grants from the Novo Nordisk Foundation and the Danish Medical Research Council.
The quadrivalent human papillomavirus (HPV) vaccine was not associated with any adverse pregnancy outcomes when inadvertently given during pregnancy, according to the findings from a nationwide Danish study.
“Our results are consistent with other evidence that does not indicate that the vaccination of pregnant women with inactivated virus, bacterial, or toxoid vaccines generally confers a higher risk of adverse pregnancy outcomes than no such vaccination. Our results also confirm and considerably expand on results from previous studies of the quadrivalent HPV vaccine,” wrote Nikolai M. Scheller, MD, of the Statens Serum Institut, Copenhagen, and his colleagues.
Quadrivalent HPV vaccination was not associated with any increase in risk for major birth defects (prevalence odds ratio, 1.19), spontaneous abortion (hazard ratio, 0.71), preterm birth (prevalence OR, 1.15), small size for gestational age (prevalence OR, 0.86), or low birth weight (prevalence OR, 1.10). It also was not associated with increased risk for stillbirth, but this outcome occurred in only two case patients and four controls, making it “impossible to draw clinically meaningful conclusions” regarding the risk for stillbirth, Dr. Scheller and his colleagues reported (N Engl J Med. 2017;376[13]:1223-33).
“Because many [adverse] pregnancy outcomes are rare, our study did not have the statistical power to assess the risks of stillbirth and specific major birth defects associated with quadrivalent HPV vaccination. Larger studies would be needed to address these outcomes,” they added.
Novo Nordisk and the Danish Medical Research Council funded the study. Dr. Scheller reported having no relevant financial disclosures; two of his coauthors reported receiving research grants from the Novo Nordisk Foundation and the Danish Medical Research Council.
Key clinical point:
Major finding: Quadrivalent HPV vaccination was not associated with any increase in risk for major birth defects (prevalence odds ratio, 1.19).
Data source: A population-based cohort study involving 581,550 pregnancies across Denmark during a 7-year period, including 1,665 in which the mother inadvertently received the HPV vaccine.
Disclosures: Novo Nordisk and the Danish Medical Research Council funded the study. Dr. Scheller reported having no relevant financial disclosures; two of his coauthors reported receiving research grants from the Novo Nordisk Foundation and the Danish Medical Research Council.
Aggressive HCC in males traced to higher serotonin
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
FROM CELLULAR & MOLECULAR GASTROENTEROLOGY & HEPATOLOGY
Key clinical point: The greater frequency and aggressiveness of hepatocellular carcinoma in men than in women might be attributable to greater synthesis and accumulation of serotonin in males.
Major finding: Serotonin levels were significantly elevated in 7 inflamed, 16 cirrhotic, and 30 cancerous livers, compared with 5 normal livers, among men but not among women.
Data source: Laboratory studies involving a zebrafish model of HCC and tissue samples from 60 human livers.
Disclosures: This study was supported by the National Medical Research Council and the Ministry of Education of Singapore. Dr. Yang and her associates reported no relevant financial disclosures.
Laparoscopic and abdominal hysterectomy yield equivalent survival
Laparoscopic hysterectomy yields equivalent disease-free and overall survival at 4.5 years, compared with abdominal hysterectomy in stage I endometrial cancer, according to a report published online March 28 in JAMA.
Several short-term advantages with the laparoscopic approach have been well documented, including less pain, less morbidity, better quality of life, decreased risk of surgery-related adverse events, and cost savings. But until now, no large international trial has demonstrated that longer-term survival outcomes are at least as good with laparoscopic as with open abdominal hysterectomy in this patient population, reported Monika Janda, PhD, of Queensland University of Technology, Brisbane (Australia) and her colleagues.
They conducted the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial, a randomized equivalence study involving 760 women treated at 20 medical centers in Australia, New Zealand, and Hong Kong during 2005-2010. The women were followed for a median of 4.5 years.
All of the women had histologically confirmed stage I adenocarcinoma of the endometrium. A total of 407 patients were randomly assigned to undergo total laparoscopic hysterectomy and 353 patients to undergo total abdominal hysterectomy. Medical comorbidities were equally distributed between the two study groups, and there were no significant between-group differences in tumor type, histologic grade, number of involved lymph nodes, or adjuvant treatments.
Disease-free survival at 4.5 years was 81.6% with laparoscopic hysterectomy and 81.3% with abdominal hysterectomy, meeting the criteria for equivalence. Overall survival at 4.5 years was 92.0% and 92.4%, respectively. Cancer recurred near the operative site in 3% of each group and at a regional or distant site in 2% or less of each group. Causes of death also were similar between the two study groups, with 56% of all deaths attributed to endometrial cancer (JAMA. 2017;317[12]:1224-33).
Of note, two patients who underwent laparoscopic surgery developed port-site metastases and two patients who underwent abdominal surgery developed metastases at the site of the abdominal wound.
The study was funded by Cancer Councils in Australia, the National Health and Medical Research Council, Cancer Australia, QLD Health, and numerous others. Dr. Janda reported having no relevant financial disclosures; one of her coauthors reported ties to the O.R. Company, SurgicalPerformance Pty, and Covidien.
This study adds to a growing body of literature that suggests laparoscopic hysterectomy is not only safe, but also the preferred modality of hysterectomy for women with endometrial cancer.
Despite the clear benefits of laparoscopic hysterectomy, the findings from the LACE trial should be interpreted in the context of the study design. Importantly, patients randomized to the study represent a highly select group of women with endometrial cancer. The study entry criteria involved a low-risk population of women with stage I tumors of endometrioid histology with a uterine size of less than 10 weeks’ gestation. In practice, laparoscopic hysterectomy is now routinely used for women with nonendometrioid histologies and in those with more advanced disease.
The LACE trial reported by Janda et al. provides confirmation that laparoscopic hysterectomy is a safe and effective treatment modality for women with early-stage endometrial cancer. The favorable short-term outcomes along with equivalent oncological outcomes make laparoscopic hysterectomy the preferred surgical modality in this setting. Even though the road to defining the benefits of laparoscopic hysterectomy has been long, efforts to promote the procedure for women with endometrial cancer should now be a priority.
Jason D. Wright, MD, is at the Herbert Irving Comprehensive Cancer Center and the department of ob.gyn. at Columbia University, New York. He reported having no relevant financial disclosures. These comments are excerpted from an accompanying editorial (JAMA 2017;317[12]:1215-6).
This study adds to a growing body of literature that suggests laparoscopic hysterectomy is not only safe, but also the preferred modality of hysterectomy for women with endometrial cancer.
Despite the clear benefits of laparoscopic hysterectomy, the findings from the LACE trial should be interpreted in the context of the study design. Importantly, patients randomized to the study represent a highly select group of women with endometrial cancer. The study entry criteria involved a low-risk population of women with stage I tumors of endometrioid histology with a uterine size of less than 10 weeks’ gestation. In practice, laparoscopic hysterectomy is now routinely used for women with nonendometrioid histologies and in those with more advanced disease.
The LACE trial reported by Janda et al. provides confirmation that laparoscopic hysterectomy is a safe and effective treatment modality for women with early-stage endometrial cancer. The favorable short-term outcomes along with equivalent oncological outcomes make laparoscopic hysterectomy the preferred surgical modality in this setting. Even though the road to defining the benefits of laparoscopic hysterectomy has been long, efforts to promote the procedure for women with endometrial cancer should now be a priority.
Jason D. Wright, MD, is at the Herbert Irving Comprehensive Cancer Center and the department of ob.gyn. at Columbia University, New York. He reported having no relevant financial disclosures. These comments are excerpted from an accompanying editorial (JAMA 2017;317[12]:1215-6).
This study adds to a growing body of literature that suggests laparoscopic hysterectomy is not only safe, but also the preferred modality of hysterectomy for women with endometrial cancer.
Despite the clear benefits of laparoscopic hysterectomy, the findings from the LACE trial should be interpreted in the context of the study design. Importantly, patients randomized to the study represent a highly select group of women with endometrial cancer. The study entry criteria involved a low-risk population of women with stage I tumors of endometrioid histology with a uterine size of less than 10 weeks’ gestation. In practice, laparoscopic hysterectomy is now routinely used for women with nonendometrioid histologies and in those with more advanced disease.
The LACE trial reported by Janda et al. provides confirmation that laparoscopic hysterectomy is a safe and effective treatment modality for women with early-stage endometrial cancer. The favorable short-term outcomes along with equivalent oncological outcomes make laparoscopic hysterectomy the preferred surgical modality in this setting. Even though the road to defining the benefits of laparoscopic hysterectomy has been long, efforts to promote the procedure for women with endometrial cancer should now be a priority.
Jason D. Wright, MD, is at the Herbert Irving Comprehensive Cancer Center and the department of ob.gyn. at Columbia University, New York. He reported having no relevant financial disclosures. These comments are excerpted from an accompanying editorial (JAMA 2017;317[12]:1215-6).
Laparoscopic hysterectomy yields equivalent disease-free and overall survival at 4.5 years, compared with abdominal hysterectomy in stage I endometrial cancer, according to a report published online March 28 in JAMA.
Several short-term advantages with the laparoscopic approach have been well documented, including less pain, less morbidity, better quality of life, decreased risk of surgery-related adverse events, and cost savings. But until now, no large international trial has demonstrated that longer-term survival outcomes are at least as good with laparoscopic as with open abdominal hysterectomy in this patient population, reported Monika Janda, PhD, of Queensland University of Technology, Brisbane (Australia) and her colleagues.
They conducted the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial, a randomized equivalence study involving 760 women treated at 20 medical centers in Australia, New Zealand, and Hong Kong during 2005-2010. The women were followed for a median of 4.5 years.
All of the women had histologically confirmed stage I adenocarcinoma of the endometrium. A total of 407 patients were randomly assigned to undergo total laparoscopic hysterectomy and 353 patients to undergo total abdominal hysterectomy. Medical comorbidities were equally distributed between the two study groups, and there were no significant between-group differences in tumor type, histologic grade, number of involved lymph nodes, or adjuvant treatments.
Disease-free survival at 4.5 years was 81.6% with laparoscopic hysterectomy and 81.3% with abdominal hysterectomy, meeting the criteria for equivalence. Overall survival at 4.5 years was 92.0% and 92.4%, respectively. Cancer recurred near the operative site in 3% of each group and at a regional or distant site in 2% or less of each group. Causes of death also were similar between the two study groups, with 56% of all deaths attributed to endometrial cancer (JAMA. 2017;317[12]:1224-33).
Of note, two patients who underwent laparoscopic surgery developed port-site metastases and two patients who underwent abdominal surgery developed metastases at the site of the abdominal wound.
The study was funded by Cancer Councils in Australia, the National Health and Medical Research Council, Cancer Australia, QLD Health, and numerous others. Dr. Janda reported having no relevant financial disclosures; one of her coauthors reported ties to the O.R. Company, SurgicalPerformance Pty, and Covidien.
Laparoscopic hysterectomy yields equivalent disease-free and overall survival at 4.5 years, compared with abdominal hysterectomy in stage I endometrial cancer, according to a report published online March 28 in JAMA.
Several short-term advantages with the laparoscopic approach have been well documented, including less pain, less morbidity, better quality of life, decreased risk of surgery-related adverse events, and cost savings. But until now, no large international trial has demonstrated that longer-term survival outcomes are at least as good with laparoscopic as with open abdominal hysterectomy in this patient population, reported Monika Janda, PhD, of Queensland University of Technology, Brisbane (Australia) and her colleagues.
They conducted the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial, a randomized equivalence study involving 760 women treated at 20 medical centers in Australia, New Zealand, and Hong Kong during 2005-2010. The women were followed for a median of 4.5 years.
All of the women had histologically confirmed stage I adenocarcinoma of the endometrium. A total of 407 patients were randomly assigned to undergo total laparoscopic hysterectomy and 353 patients to undergo total abdominal hysterectomy. Medical comorbidities were equally distributed between the two study groups, and there were no significant between-group differences in tumor type, histologic grade, number of involved lymph nodes, or adjuvant treatments.
Disease-free survival at 4.5 years was 81.6% with laparoscopic hysterectomy and 81.3% with abdominal hysterectomy, meeting the criteria for equivalence. Overall survival at 4.5 years was 92.0% and 92.4%, respectively. Cancer recurred near the operative site in 3% of each group and at a regional or distant site in 2% or less of each group. Causes of death also were similar between the two study groups, with 56% of all deaths attributed to endometrial cancer (JAMA. 2017;317[12]:1224-33).
Of note, two patients who underwent laparoscopic surgery developed port-site metastases and two patients who underwent abdominal surgery developed metastases at the site of the abdominal wound.
The study was funded by Cancer Councils in Australia, the National Health and Medical Research Council, Cancer Australia, QLD Health, and numerous others. Dr. Janda reported having no relevant financial disclosures; one of her coauthors reported ties to the O.R. Company, SurgicalPerformance Pty, and Covidien.
FROM JAMA
Key clinical point:
Major finding: Disease-free survival at 4.5 years was 81.6% with laparoscopic hysterectomy and 81.3% with abdominal hysterectomy.
Data source: An international, randomized, phase III equivalence trial involving 760 women treated with total abdominal or total laparoscopic hysterectomy.
Disclosures: The study was funded by Cancer Councils in Australia, the National Health and Medical Research Council, Cancer Australia, QLD Health, and others. Dr. Janda reported having no relevant financial disclosures; one of her coauthors reported ties to the O.R. Company, SurgicalPerformance Pty, and Covidien.
USPSTF: No recommendation on screening for celiac disease
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
FROM JAMA
Key clinical point: The current evidence is insufficient for the USPSTF to recommend either for or against routine screening of asymptomatic people for celiac disease.
Major finding: Only 4 studies out of the 3,036 that were examined addressed the question of screening adequately.
Data source: An assessment of the benefits and harms of screening based on a review of four studies.
Disclosures: The USPSTF’s work is supported by the U.S. Agency for Healthcare Research and Quality. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.