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USPSTF: Offer behavioral counseling to prevent cardiovascular disease
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Refer overweight or obese patients at risk of cardiovascular disease for intensive behavioral counseling.
Major Finding: Intensive behavioral counseling interventions made small but important changes in several intermediate health outcomes, with total cholesterol levels decreasing by about 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, fasting glucose levels decreasing by 1-3 mg/dL, and weight decreasing by a mean of 3 kg.
Data Source: An update and refinement of a 2003 USPSTF recommendation on dietary counseling for overweight/obese adults who have additional risk factors for CVD, based on a comprehensive review of the literature.
Disclosures: The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
New cholesterol guideline outperforms ATP III
The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.
The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).
In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.
The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.
Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).
"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).
Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.
"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.
Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.
The seminal findings of Dr. Johnson and Dr. Dowe are important because they strongly support the results of previous studies that the 2001 ATP III guidelines undertreated patients with statins – especially younger, high-risk patients who stood to gain the most from this therapy – resulting from their use of LDL cholesterol goals. The new guidelines appear to reduce this critical limitation.
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The new guidelines also recommend statin therapy to fewer patients who don’t have demonstrable disease than did the old guidelines. In short, the 2013 ACC/AHA guidelines appear to be a major clinical and conceptual improvement over the older ones.
There are, however, limitations to keep in mind. Because the study population was referred for CT angiography, it was likely at higher than average risk. The most important and inescapable limitation is that plaque burden is a good but imperfect predictor of future coronary events.
This study asks the fundamental question of whether guidelines are really distilled wisdom or simply working hypotheses. Because they now determine how health care is measured and reimbursed, guidelines should be validated more by science and less by the opinions of experts and medical societies.
Robert A. Vogel, M.D., is with the cardiology section at the Veterans Affairs Medical Center in Denver. He also is the national coordinator of the ODYSSEY Outcomes clinical trial sponsored by Sanofi-Aventis. These remarks are from an accompanying editorial (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.06.1168]). Dr. Vogel reported no other financial conflicts of interest.
The seminal findings of Dr. Johnson and Dr. Dowe are important because they strongly support the results of previous studies that the 2001 ATP III guidelines undertreated patients with statins – especially younger, high-risk patients who stood to gain the most from this therapy – resulting from their use of LDL cholesterol goals. The new guidelines appear to reduce this critical limitation.
|
|
The new guidelines also recommend statin therapy to fewer patients who don’t have demonstrable disease than did the old guidelines. In short, the 2013 ACC/AHA guidelines appear to be a major clinical and conceptual improvement over the older ones.
There are, however, limitations to keep in mind. Because the study population was referred for CT angiography, it was likely at higher than average risk. The most important and inescapable limitation is that plaque burden is a good but imperfect predictor of future coronary events.
This study asks the fundamental question of whether guidelines are really distilled wisdom or simply working hypotheses. Because they now determine how health care is measured and reimbursed, guidelines should be validated more by science and less by the opinions of experts and medical societies.
Robert A. Vogel, M.D., is with the cardiology section at the Veterans Affairs Medical Center in Denver. He also is the national coordinator of the ODYSSEY Outcomes clinical trial sponsored by Sanofi-Aventis. These remarks are from an accompanying editorial (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.06.1168]). Dr. Vogel reported no other financial conflicts of interest.
The seminal findings of Dr. Johnson and Dr. Dowe are important because they strongly support the results of previous studies that the 2001 ATP III guidelines undertreated patients with statins – especially younger, high-risk patients who stood to gain the most from this therapy – resulting from their use of LDL cholesterol goals. The new guidelines appear to reduce this critical limitation.
|
|
The new guidelines also recommend statin therapy to fewer patients who don’t have demonstrable disease than did the old guidelines. In short, the 2013 ACC/AHA guidelines appear to be a major clinical and conceptual improvement over the older ones.
There are, however, limitations to keep in mind. Because the study population was referred for CT angiography, it was likely at higher than average risk. The most important and inescapable limitation is that plaque burden is a good but imperfect predictor of future coronary events.
This study asks the fundamental question of whether guidelines are really distilled wisdom or simply working hypotheses. Because they now determine how health care is measured and reimbursed, guidelines should be validated more by science and less by the opinions of experts and medical societies.
Robert A. Vogel, M.D., is with the cardiology section at the Veterans Affairs Medical Center in Denver. He also is the national coordinator of the ODYSSEY Outcomes clinical trial sponsored by Sanofi-Aventis. These remarks are from an accompanying editorial (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.06.1168]). Dr. Vogel reported no other financial conflicts of interest.
The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.
The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).
In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.
The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.
Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).
"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).
Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.
"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.
Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.
The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.
The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).
In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.
The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.
Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).
"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).
Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.
"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.
Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: The 2013 ACC/AHA guideline matches statin use to patients’ total plaque burden better than ATP III, while increasing statin assignment modestly.
Major Finding: Among all patients who proved to have heavy plaque on CT angiography, 92% would have been advised appropriately to use statin therapy according to the 2013 guidelines, compared with 53% who would have been so advised according to the ATP III guidelines.
Data Source: A retrospective study involving 3,076 adults seen in a 5-year period for whom the initiation of statin therapy was either recommended or not recommended using both the ATP III guidelines and the 2013 ACC/AHA guidelines for cholesterol therapy.
Disclosures: Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.
High-dose Flu Vaccine More Effective for Elderly
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
More patients with multidrug-resistant TB respond quickly to bedaquiline
Adding bedaquiline to a five-drug background regimen for multidrug-resistant pulmonary tuberculosis significantly accelerated the time at which sputum cultures showed clearance of Mycobacterium tuberculosis in a phase IIb clinical trial, which was published online Aug. 21 in the New England Journal of Medicine.
The addition of 6 months of oral bedaquiline – a diarylquinoline that inhibits mycobacterial ATP synthase and depletes cellular energy stores – also significantly increased the number of patients who achieved such culture conversion (a surrogate for clinical cure), compared with adding placebo, in this industry-sponsored study. Bedaquiline "is the first antituberculosis drug with a new mechanism of action to be approved for use in multidrug-resistant TB in 40 years," said Dr. Andreas H. Diacon of the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research at Stellenbosch University in Cape Town, South Africa, and his associates.
Bedaquiline was approved in 2012 under the Food and Drug Administration’s accelerated-approval regulations for drugs that provide meaningful therapeutic benefit over existing therapies for serious or life-threatening conditions. The drug is approved only for patients for whom an effective treatment regimen cannot be constructed without it, a population in whom the benefits outweigh the risks.
In the trial, 160 adults with multidrug-resistant pulmonary TB were randomly assigned to receive either oral bedaquiline (79 patients) or matching placebo tablets (81 patients) for 24 weeks at medical centers in Brazil, India, Latvia, Peru, the Philippines, Russia, South Africa, and Thailand, in addition to the five-drug background regimen of antituberculosis drugs preferred at each location. They continued the background therapy for a further 96 weeks and had a final follow-up exam at the conclusion of that treatment. Sixty participants (38%) left the study prematurely, usually because of withdrawal of consent, adverse effects, nonadherence, loss to follow-up, and pregnancy. The number of and reasons for these discontinuations were similar between the two study groups.
The primary endpoint of the study was the median time to sputum conversion. This was significantly faster in the intervention group (83 days) than in the control group (125 days) in both the modified intention-to-treat analysis and the full intention-to-treat analysis. Moreover, more patients in the intervention group (79%) than in the placebo group (58%) showed culture conversion at 24 weeks, as well as at 120 weeks (62% vs 44%). And according to the World Health Organization definition of "cure," nearly twice as many patients in the bedaquiline group (58%) were cured as in the placebo group (32%) at 120 weeks, Dr. Diacon and his associates said (N. Engl. J. Med. 2014;371:723-32 [doi:10.1056/NEJMoa1313865]).
Fewer patients taking bedaquiline (2) than taking placebo (16) developed new resistance to at least one antituberculosis agent during the study. Rates, types, and severity of adverse events were comparable between the two study groups. However, mortality was significantly higher with bedaquiline (10 patients, 13% mortality) than with placebo (2 patients, 2% mortality), for reasons that are not yet understood but do not appear to be related to the study drug.
"A planned phase III study will enroll a larger number of patients, including HIV-positive patients receiving antiretroviral therapy," the investigators noted.
This study was funded by Janssen Pharmaceuticals. Dr. Diacon reported no financial conflicts of interest. His associates reported ties to Janssen; to its parent company, Johnson & Johnson; and to Quintiles.
The Food and Drug Administration approved the limited use of bedaquiline despite the unexpected finding of significantly increased mortality in the intervention group (13%) than in the control group (2%), because the length of time between the last receipt of bedaquiline and death – 329 days – makes it difficult to discern a mechanism by which the drug could be directly related to the deaths, even if bedaquiline’s long half-life is taken into consideration.
This imbalance in mortality is an important concern. However, 1 of the 10 deaths that occurred in patients who received bedaquiline was because of a motor vehicle accident, 5 were from disease progression (as were both deaths in the placebo group), and the remaining 4 had no apparent commonality. A confirmatory trial, a condition of the accelerated approval of the drug, should shed more light on this discrepancy in mortality.
Dr. Edward Cox and Dr. Katherine Laessig are in the Office of Antimicrobial Products and the Office of New Drugs, the Center for Drug Evaluation and Research, at the FDA. They made their remarks in a perspective piece accompanying Dr. Diacon’s report (N. Engl. J. Med. 2014;371:689-91 [doi:10.1056/NEJMp1314385]). They reported no financial conflicts of interest.
The Food and Drug Administration approved the limited use of bedaquiline despite the unexpected finding of significantly increased mortality in the intervention group (13%) than in the control group (2%), because the length of time between the last receipt of bedaquiline and death – 329 days – makes it difficult to discern a mechanism by which the drug could be directly related to the deaths, even if bedaquiline’s long half-life is taken into consideration.
This imbalance in mortality is an important concern. However, 1 of the 10 deaths that occurred in patients who received bedaquiline was because of a motor vehicle accident, 5 were from disease progression (as were both deaths in the placebo group), and the remaining 4 had no apparent commonality. A confirmatory trial, a condition of the accelerated approval of the drug, should shed more light on this discrepancy in mortality.
Dr. Edward Cox and Dr. Katherine Laessig are in the Office of Antimicrobial Products and the Office of New Drugs, the Center for Drug Evaluation and Research, at the FDA. They made their remarks in a perspective piece accompanying Dr. Diacon’s report (N. Engl. J. Med. 2014;371:689-91 [doi:10.1056/NEJMp1314385]). They reported no financial conflicts of interest.
The Food and Drug Administration approved the limited use of bedaquiline despite the unexpected finding of significantly increased mortality in the intervention group (13%) than in the control group (2%), because the length of time between the last receipt of bedaquiline and death – 329 days – makes it difficult to discern a mechanism by which the drug could be directly related to the deaths, even if bedaquiline’s long half-life is taken into consideration.
This imbalance in mortality is an important concern. However, 1 of the 10 deaths that occurred in patients who received bedaquiline was because of a motor vehicle accident, 5 were from disease progression (as were both deaths in the placebo group), and the remaining 4 had no apparent commonality. A confirmatory trial, a condition of the accelerated approval of the drug, should shed more light on this discrepancy in mortality.
Dr. Edward Cox and Dr. Katherine Laessig are in the Office of Antimicrobial Products and the Office of New Drugs, the Center for Drug Evaluation and Research, at the FDA. They made their remarks in a perspective piece accompanying Dr. Diacon’s report (N. Engl. J. Med. 2014;371:689-91 [doi:10.1056/NEJMp1314385]). They reported no financial conflicts of interest.
Adding bedaquiline to a five-drug background regimen for multidrug-resistant pulmonary tuberculosis significantly accelerated the time at which sputum cultures showed clearance of Mycobacterium tuberculosis in a phase IIb clinical trial, which was published online Aug. 21 in the New England Journal of Medicine.
The addition of 6 months of oral bedaquiline – a diarylquinoline that inhibits mycobacterial ATP synthase and depletes cellular energy stores – also significantly increased the number of patients who achieved such culture conversion (a surrogate for clinical cure), compared with adding placebo, in this industry-sponsored study. Bedaquiline "is the first antituberculosis drug with a new mechanism of action to be approved for use in multidrug-resistant TB in 40 years," said Dr. Andreas H. Diacon of the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research at Stellenbosch University in Cape Town, South Africa, and his associates.
Bedaquiline was approved in 2012 under the Food and Drug Administration’s accelerated-approval regulations for drugs that provide meaningful therapeutic benefit over existing therapies for serious or life-threatening conditions. The drug is approved only for patients for whom an effective treatment regimen cannot be constructed without it, a population in whom the benefits outweigh the risks.
In the trial, 160 adults with multidrug-resistant pulmonary TB were randomly assigned to receive either oral bedaquiline (79 patients) or matching placebo tablets (81 patients) for 24 weeks at medical centers in Brazil, India, Latvia, Peru, the Philippines, Russia, South Africa, and Thailand, in addition to the five-drug background regimen of antituberculosis drugs preferred at each location. They continued the background therapy for a further 96 weeks and had a final follow-up exam at the conclusion of that treatment. Sixty participants (38%) left the study prematurely, usually because of withdrawal of consent, adverse effects, nonadherence, loss to follow-up, and pregnancy. The number of and reasons for these discontinuations were similar between the two study groups.
The primary endpoint of the study was the median time to sputum conversion. This was significantly faster in the intervention group (83 days) than in the control group (125 days) in both the modified intention-to-treat analysis and the full intention-to-treat analysis. Moreover, more patients in the intervention group (79%) than in the placebo group (58%) showed culture conversion at 24 weeks, as well as at 120 weeks (62% vs 44%). And according to the World Health Organization definition of "cure," nearly twice as many patients in the bedaquiline group (58%) were cured as in the placebo group (32%) at 120 weeks, Dr. Diacon and his associates said (N. Engl. J. Med. 2014;371:723-32 [doi:10.1056/NEJMoa1313865]).
Fewer patients taking bedaquiline (2) than taking placebo (16) developed new resistance to at least one antituberculosis agent during the study. Rates, types, and severity of adverse events were comparable between the two study groups. However, mortality was significantly higher with bedaquiline (10 patients, 13% mortality) than with placebo (2 patients, 2% mortality), for reasons that are not yet understood but do not appear to be related to the study drug.
"A planned phase III study will enroll a larger number of patients, including HIV-positive patients receiving antiretroviral therapy," the investigators noted.
This study was funded by Janssen Pharmaceuticals. Dr. Diacon reported no financial conflicts of interest. His associates reported ties to Janssen; to its parent company, Johnson & Johnson; and to Quintiles.
Adding bedaquiline to a five-drug background regimen for multidrug-resistant pulmonary tuberculosis significantly accelerated the time at which sputum cultures showed clearance of Mycobacterium tuberculosis in a phase IIb clinical trial, which was published online Aug. 21 in the New England Journal of Medicine.
The addition of 6 months of oral bedaquiline – a diarylquinoline that inhibits mycobacterial ATP synthase and depletes cellular energy stores – also significantly increased the number of patients who achieved such culture conversion (a surrogate for clinical cure), compared with adding placebo, in this industry-sponsored study. Bedaquiline "is the first antituberculosis drug with a new mechanism of action to be approved for use in multidrug-resistant TB in 40 years," said Dr. Andreas H. Diacon of the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research at Stellenbosch University in Cape Town, South Africa, and his associates.
Bedaquiline was approved in 2012 under the Food and Drug Administration’s accelerated-approval regulations for drugs that provide meaningful therapeutic benefit over existing therapies for serious or life-threatening conditions. The drug is approved only for patients for whom an effective treatment regimen cannot be constructed without it, a population in whom the benefits outweigh the risks.
In the trial, 160 adults with multidrug-resistant pulmonary TB were randomly assigned to receive either oral bedaquiline (79 patients) or matching placebo tablets (81 patients) for 24 weeks at medical centers in Brazil, India, Latvia, Peru, the Philippines, Russia, South Africa, and Thailand, in addition to the five-drug background regimen of antituberculosis drugs preferred at each location. They continued the background therapy for a further 96 weeks and had a final follow-up exam at the conclusion of that treatment. Sixty participants (38%) left the study prematurely, usually because of withdrawal of consent, adverse effects, nonadherence, loss to follow-up, and pregnancy. The number of and reasons for these discontinuations were similar between the two study groups.
The primary endpoint of the study was the median time to sputum conversion. This was significantly faster in the intervention group (83 days) than in the control group (125 days) in both the modified intention-to-treat analysis and the full intention-to-treat analysis. Moreover, more patients in the intervention group (79%) than in the placebo group (58%) showed culture conversion at 24 weeks, as well as at 120 weeks (62% vs 44%). And according to the World Health Organization definition of "cure," nearly twice as many patients in the bedaquiline group (58%) were cured as in the placebo group (32%) at 120 weeks, Dr. Diacon and his associates said (N. Engl. J. Med. 2014;371:723-32 [doi:10.1056/NEJMoa1313865]).
Fewer patients taking bedaquiline (2) than taking placebo (16) developed new resistance to at least one antituberculosis agent during the study. Rates, types, and severity of adverse events were comparable between the two study groups. However, mortality was significantly higher with bedaquiline (10 patients, 13% mortality) than with placebo (2 patients, 2% mortality), for reasons that are not yet understood but do not appear to be related to the study drug.
"A planned phase III study will enroll a larger number of patients, including HIV-positive patients receiving antiretroviral therapy," the investigators noted.
This study was funded by Janssen Pharmaceuticals. Dr. Diacon reported no financial conflicts of interest. His associates reported ties to Janssen; to its parent company, Johnson & Johnson; and to Quintiles.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Bedaquiline may offer an alternative treatment for multidrug-resistant TB.
Major finding: The primary endpoint of the study – the median time to sputum conversion – was significantly faster in the intervention group (83 days) than in the control group (125 days), and more patients in the intervention group (79%) than in the placebo group (58%) showed culture conversion at 24 weeks, as well as at 120 weeks (62% vs 44%).
Data source: A randomized, double-blind, placebo-controlled, phase IIb clinical trial involving 160 adults with multidrug-resistant pulmonary TB treated for 24 weeks in eight countries.
Disclosures: This study was funded by Janssen Pharmaceuticals. Dr. Diacon reported no financial conflicts of interest. His associates reported ties to Janssen; to its parent company, Johnson & Johnson; and to Quintiles.
Too much reliance on oximetry in bronchiolitis
Among infants presenting to an emergency department with mild to moderate bronchiolitis, those whose pulse oximetry readings were artificially elevated by 3 percentage points were significantly less likely to be hospitalized than were comparable patients whose pulse oximetry readings were unaltered, according to a report published online Aug. 19 in JAMA.
The accuracy of most oxygen-saturation monitors is approximately plus or minus 2%, and oximetry readings are subject to multiple sources of error, so "the actual physiological difference between the true and altered oximetry measurements in our study was of minor importance. Yet this difference had significant implications for hospitalization," said Dr. Suzanne Schuh, a pediatrician at the Hospital for Sick Children, Toronto, and her associates.
Their findings indicate that clinicians are relying too heavily on tiny differences in a single laboratory parameter – the pulse oximetry reading – to make clinical decisions in this patient population. The results of their experiment further suggest that the monitoring of oxygen saturation in this setting may need to be reevaluated, Dr. Schuh and her colleagues wrote (JAMA 2014;312:712-8).
The introduction and routine use of pulse oximetry in infants with mild to moderate bronchiolitis in the 1980s and 1990s coincided with more than a doubling of hospitalization rates for the disorder. Moreover, the somewhat arbitrary cutoff point of 90% oxygen saturation, which triggers the use of supplemental oxygen, has never been shown to correlate with bronchiolitis progression, yet many mildly ill infants are hospitalized solely because of that reading. Even expert opinion "cautions against overreliance on oximetry and argues for the use of clinical judgment when making disposition determinations," the investigators noted.
They performed this prospective, randomized, double-blind trial to determine whether artificially raising the pulse oximetry reading displayed to emergency department (ED) clinicians by an amount of "minor importance" would lead to fewer unnecessary hospitalizations in 213 otherwise healthy infants (aged 4-12 months) presenting to a single tertiary care pediatric ED during a 5-year period. The 13 physicians who cared for these patients were blinded to the study protocol and ordered supplemental oxygen and pharmacotherapy at their own discretion.
All the infants had a true oxygen saturation of 88% or higher, as well as comparable clinical characteristics and Respiratory Disease Assessment Instrument scores. The oxygen saturation reading was accurately displayed to treating clinicians in the 108 infants who were randomly assigned to "true" oximetry. In the other 105 infants, the oxygen saturation reading was increased by 3 points and displayed to treating clinicians.
All the infants in the study underwent concealed continuous oximetry for safety reasons. These hidden monitors were programmed to sound an alarm if oxygen saturation dropped to less than 92%, which would prompt a thorough clinical reassessment.
The primary outcome of the study was hospitalization for bronchiolitis within 72 hours of enrollment due to concerns about respiratory distress. This occurred in 41% of infants in the true-oximetry group, compared with only 25% of those whose oximetry reading was artificially increased – a significant 16% difference. Yet the medical outcomes of the two study groups were comparable, Dr. Schuh and her associates reported.
"Our results suggest an even lower cutoff might be appropriate and that among children with saturation levels of 88% and higher, disposition determination should be based primarily on the degree of respiratory distress and hydration status, rather than on a particular saturation value," they said.
This study was supported by the Thrasher Research Fund and the Physicians’ Services Incorporated Foundation; Masimo provided the oximeters but played no role in the design or conduct of the study. Dr. Schuh and her associates reported that they had no financial conflicts of interest.
The conditions of this experiment "reflect the experience of many physicians who have been bedeviled by the reliance on oxygen saturation readings to make clinical decisions, particularly for infants with a self-limited disease who are mildly ill," commented Robert Vinci, M.D., and Howard Bauchner, M.D.
"It is now clear that the oxygen saturation reading can influence decision-making in ways that many physicians have thought likely – overreliance on physiologic information of uncertain importance derived from a medical device," they noted.
Dr. Vinci is a pediatrician at Boston Medical Center. Dr. Bauchner is editor in chief of JAMA. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Schuh’s report (JAMA 2014;312:699-700).
The conditions of this experiment "reflect the experience of many physicians who have been bedeviled by the reliance on oxygen saturation readings to make clinical decisions, particularly for infants with a self-limited disease who are mildly ill," commented Robert Vinci, M.D., and Howard Bauchner, M.D.
"It is now clear that the oxygen saturation reading can influence decision-making in ways that many physicians have thought likely – overreliance on physiologic information of uncertain importance derived from a medical device," they noted.
Dr. Vinci is a pediatrician at Boston Medical Center. Dr. Bauchner is editor in chief of JAMA. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Schuh’s report (JAMA 2014;312:699-700).
The conditions of this experiment "reflect the experience of many physicians who have been bedeviled by the reliance on oxygen saturation readings to make clinical decisions, particularly for infants with a self-limited disease who are mildly ill," commented Robert Vinci, M.D., and Howard Bauchner, M.D.
"It is now clear that the oxygen saturation reading can influence decision-making in ways that many physicians have thought likely – overreliance on physiologic information of uncertain importance derived from a medical device," they noted.
Dr. Vinci is a pediatrician at Boston Medical Center. Dr. Bauchner is editor in chief of JAMA. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Schuh’s report (JAMA 2014;312:699-700).
Among infants presenting to an emergency department with mild to moderate bronchiolitis, those whose pulse oximetry readings were artificially elevated by 3 percentage points were significantly less likely to be hospitalized than were comparable patients whose pulse oximetry readings were unaltered, according to a report published online Aug. 19 in JAMA.
The accuracy of most oxygen-saturation monitors is approximately plus or minus 2%, and oximetry readings are subject to multiple sources of error, so "the actual physiological difference between the true and altered oximetry measurements in our study was of minor importance. Yet this difference had significant implications for hospitalization," said Dr. Suzanne Schuh, a pediatrician at the Hospital for Sick Children, Toronto, and her associates.
Their findings indicate that clinicians are relying too heavily on tiny differences in a single laboratory parameter – the pulse oximetry reading – to make clinical decisions in this patient population. The results of their experiment further suggest that the monitoring of oxygen saturation in this setting may need to be reevaluated, Dr. Schuh and her colleagues wrote (JAMA 2014;312:712-8).
The introduction and routine use of pulse oximetry in infants with mild to moderate bronchiolitis in the 1980s and 1990s coincided with more than a doubling of hospitalization rates for the disorder. Moreover, the somewhat arbitrary cutoff point of 90% oxygen saturation, which triggers the use of supplemental oxygen, has never been shown to correlate with bronchiolitis progression, yet many mildly ill infants are hospitalized solely because of that reading. Even expert opinion "cautions against overreliance on oximetry and argues for the use of clinical judgment when making disposition determinations," the investigators noted.
They performed this prospective, randomized, double-blind trial to determine whether artificially raising the pulse oximetry reading displayed to emergency department (ED) clinicians by an amount of "minor importance" would lead to fewer unnecessary hospitalizations in 213 otherwise healthy infants (aged 4-12 months) presenting to a single tertiary care pediatric ED during a 5-year period. The 13 physicians who cared for these patients were blinded to the study protocol and ordered supplemental oxygen and pharmacotherapy at their own discretion.
All the infants had a true oxygen saturation of 88% or higher, as well as comparable clinical characteristics and Respiratory Disease Assessment Instrument scores. The oxygen saturation reading was accurately displayed to treating clinicians in the 108 infants who were randomly assigned to "true" oximetry. In the other 105 infants, the oxygen saturation reading was increased by 3 points and displayed to treating clinicians.
All the infants in the study underwent concealed continuous oximetry for safety reasons. These hidden monitors were programmed to sound an alarm if oxygen saturation dropped to less than 92%, which would prompt a thorough clinical reassessment.
The primary outcome of the study was hospitalization for bronchiolitis within 72 hours of enrollment due to concerns about respiratory distress. This occurred in 41% of infants in the true-oximetry group, compared with only 25% of those whose oximetry reading was artificially increased – a significant 16% difference. Yet the medical outcomes of the two study groups were comparable, Dr. Schuh and her associates reported.
"Our results suggest an even lower cutoff might be appropriate and that among children with saturation levels of 88% and higher, disposition determination should be based primarily on the degree of respiratory distress and hydration status, rather than on a particular saturation value," they said.
This study was supported by the Thrasher Research Fund and the Physicians’ Services Incorporated Foundation; Masimo provided the oximeters but played no role in the design or conduct of the study. Dr. Schuh and her associates reported that they had no financial conflicts of interest.
Among infants presenting to an emergency department with mild to moderate bronchiolitis, those whose pulse oximetry readings were artificially elevated by 3 percentage points were significantly less likely to be hospitalized than were comparable patients whose pulse oximetry readings were unaltered, according to a report published online Aug. 19 in JAMA.
The accuracy of most oxygen-saturation monitors is approximately plus or minus 2%, and oximetry readings are subject to multiple sources of error, so "the actual physiological difference between the true and altered oximetry measurements in our study was of minor importance. Yet this difference had significant implications for hospitalization," said Dr. Suzanne Schuh, a pediatrician at the Hospital for Sick Children, Toronto, and her associates.
Their findings indicate that clinicians are relying too heavily on tiny differences in a single laboratory parameter – the pulse oximetry reading – to make clinical decisions in this patient population. The results of their experiment further suggest that the monitoring of oxygen saturation in this setting may need to be reevaluated, Dr. Schuh and her colleagues wrote (JAMA 2014;312:712-8).
The introduction and routine use of pulse oximetry in infants with mild to moderate bronchiolitis in the 1980s and 1990s coincided with more than a doubling of hospitalization rates for the disorder. Moreover, the somewhat arbitrary cutoff point of 90% oxygen saturation, which triggers the use of supplemental oxygen, has never been shown to correlate with bronchiolitis progression, yet many mildly ill infants are hospitalized solely because of that reading. Even expert opinion "cautions against overreliance on oximetry and argues for the use of clinical judgment when making disposition determinations," the investigators noted.
They performed this prospective, randomized, double-blind trial to determine whether artificially raising the pulse oximetry reading displayed to emergency department (ED) clinicians by an amount of "minor importance" would lead to fewer unnecessary hospitalizations in 213 otherwise healthy infants (aged 4-12 months) presenting to a single tertiary care pediatric ED during a 5-year period. The 13 physicians who cared for these patients were blinded to the study protocol and ordered supplemental oxygen and pharmacotherapy at their own discretion.
All the infants had a true oxygen saturation of 88% or higher, as well as comparable clinical characteristics and Respiratory Disease Assessment Instrument scores. The oxygen saturation reading was accurately displayed to treating clinicians in the 108 infants who were randomly assigned to "true" oximetry. In the other 105 infants, the oxygen saturation reading was increased by 3 points and displayed to treating clinicians.
All the infants in the study underwent concealed continuous oximetry for safety reasons. These hidden monitors were programmed to sound an alarm if oxygen saturation dropped to less than 92%, which would prompt a thorough clinical reassessment.
The primary outcome of the study was hospitalization for bronchiolitis within 72 hours of enrollment due to concerns about respiratory distress. This occurred in 41% of infants in the true-oximetry group, compared with only 25% of those whose oximetry reading was artificially increased – a significant 16% difference. Yet the medical outcomes of the two study groups were comparable, Dr. Schuh and her associates reported.
"Our results suggest an even lower cutoff might be appropriate and that among children with saturation levels of 88% and higher, disposition determination should be based primarily on the degree of respiratory distress and hydration status, rather than on a particular saturation value," they said.
This study was supported by the Thrasher Research Fund and the Physicians’ Services Incorporated Foundation; Masimo provided the oximeters but played no role in the design or conduct of the study. Dr. Schuh and her associates reported that they had no financial conflicts of interest.
FROM JAMA
Key clinical point: Physicians may be overrelying on pulse oximetry readings when evaluating infants who present to the ED with mild to moderate bronchiolitis.
Major finding: The primary outcome of the study – hospitalization for bronchiolitis within 72 hours of enrollment due to concerns about respiratory distress – occurred in 41% of infants in the true-oximetry group, compared with only 25% of those whose oximetry reading was artificially increased.
Data source: A prospective, randomized, double-blind clinical trial assessing the medical management of 213 infants presenting to a single tertiary-care ED with mild to moderate bronchiolitis during a 5-year period.
Disclosures: This study was supported by the Thrasher Research Fund and the Physicians’ Services Incorporated Foundation; Masimo provided the oximeters but played no role in the design or conduct of the study. Dr. Schuh and her associates reported that they had no financial conflicts of interest.
Many acute HF patients overuse emergency departments
Approximately one-third of patients who present to the emergency department with acute heart failure syndrome are frequent ED users, and they account for "an enormous burden of health care utilization and expenditures," according to a report published online Aug. 19 in Circulation: Cardiovascular Quality and Outcomes.
Frequent ED use for this condition reflects a failure in secondary prevention and is considered to be preventable with good-quality longitudinal management, said Dr. Kohei Hasegawa of the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School, Boston.
Dr. Hasegawa and his colleagues assessed the frequency of ED usage by analyzing information from two large databases, focusing on 113,033 adults who made 175,491 ED visits for acute HF syndrome in California and Florida during a 1-year period. Most of these patients (69%) required only one ED visit during that time, but the remaining 31% were frequent users (overusers) who had at least two visits, accounted for more than half of all ED visits and hospitalizations for this condition, and accounted for 58% of all near-fatal events.
In this study, if recurrent ED visits after the index visit had been prevented by better quality longitudinal care, "up to 62,458 ED visits and 53,234 hospitalizations would have been saved annually in [these] two states alone. In terms of expenditures, this would have saved $1.06 billion, in Florida alone," Dr. Hasegawa and his associates said (Circ. Cardiovasc. Qual. Outcomes 2014 Aug. 19 [doi: 10.1161/Circoutcomes.114.000949]).
Frequent users were more likely to be male than female; to be black or Hispanic than other races/ethnicities; to have several markers of low socioeconomic status such as low income and Medicaid insurance; and to have several comorbid conditions such as chronic pulmonary disease, renal failure, diabetes, depression, and drug abuse.
"Although the pathway through which socioeconomic status and health care–related factors affect health care utilization is undoubtedly complex, studies in other chronic conditions suggest that less self-management education and limited access to preventive care in this population might lead to a heavier reliance on episodic treatment in the ED," the investigators said.
This study was supported in part by the Eleanor and Miles Shore Fellowship Program and the Honjo International Scholarship Foundation. Dr. Hasegawa and his associates reported no financial conflicts of interest.
Approximately one-third of patients who present to the emergency department with acute heart failure syndrome are frequent ED users, and they account for "an enormous burden of health care utilization and expenditures," according to a report published online Aug. 19 in Circulation: Cardiovascular Quality and Outcomes.
Frequent ED use for this condition reflects a failure in secondary prevention and is considered to be preventable with good-quality longitudinal management, said Dr. Kohei Hasegawa of the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School, Boston.
Dr. Hasegawa and his colleagues assessed the frequency of ED usage by analyzing information from two large databases, focusing on 113,033 adults who made 175,491 ED visits for acute HF syndrome in California and Florida during a 1-year period. Most of these patients (69%) required only one ED visit during that time, but the remaining 31% were frequent users (overusers) who had at least two visits, accounted for more than half of all ED visits and hospitalizations for this condition, and accounted for 58% of all near-fatal events.
In this study, if recurrent ED visits after the index visit had been prevented by better quality longitudinal care, "up to 62,458 ED visits and 53,234 hospitalizations would have been saved annually in [these] two states alone. In terms of expenditures, this would have saved $1.06 billion, in Florida alone," Dr. Hasegawa and his associates said (Circ. Cardiovasc. Qual. Outcomes 2014 Aug. 19 [doi: 10.1161/Circoutcomes.114.000949]).
Frequent users were more likely to be male than female; to be black or Hispanic than other races/ethnicities; to have several markers of low socioeconomic status such as low income and Medicaid insurance; and to have several comorbid conditions such as chronic pulmonary disease, renal failure, diabetes, depression, and drug abuse.
"Although the pathway through which socioeconomic status and health care–related factors affect health care utilization is undoubtedly complex, studies in other chronic conditions suggest that less self-management education and limited access to preventive care in this population might lead to a heavier reliance on episodic treatment in the ED," the investigators said.
This study was supported in part by the Eleanor and Miles Shore Fellowship Program and the Honjo International Scholarship Foundation. Dr. Hasegawa and his associates reported no financial conflicts of interest.
Approximately one-third of patients who present to the emergency department with acute heart failure syndrome are frequent ED users, and they account for "an enormous burden of health care utilization and expenditures," according to a report published online Aug. 19 in Circulation: Cardiovascular Quality and Outcomes.
Frequent ED use for this condition reflects a failure in secondary prevention and is considered to be preventable with good-quality longitudinal management, said Dr. Kohei Hasegawa of the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School, Boston.
Dr. Hasegawa and his colleagues assessed the frequency of ED usage by analyzing information from two large databases, focusing on 113,033 adults who made 175,491 ED visits for acute HF syndrome in California and Florida during a 1-year period. Most of these patients (69%) required only one ED visit during that time, but the remaining 31% were frequent users (overusers) who had at least two visits, accounted for more than half of all ED visits and hospitalizations for this condition, and accounted for 58% of all near-fatal events.
In this study, if recurrent ED visits after the index visit had been prevented by better quality longitudinal care, "up to 62,458 ED visits and 53,234 hospitalizations would have been saved annually in [these] two states alone. In terms of expenditures, this would have saved $1.06 billion, in Florida alone," Dr. Hasegawa and his associates said (Circ. Cardiovasc. Qual. Outcomes 2014 Aug. 19 [doi: 10.1161/Circoutcomes.114.000949]).
Frequent users were more likely to be male than female; to be black or Hispanic than other races/ethnicities; to have several markers of low socioeconomic status such as low income and Medicaid insurance; and to have several comorbid conditions such as chronic pulmonary disease, renal failure, diabetes, depression, and drug abuse.
"Although the pathway through which socioeconomic status and health care–related factors affect health care utilization is undoubtedly complex, studies in other chronic conditions suggest that less self-management education and limited access to preventive care in this population might lead to a heavier reliance on episodic treatment in the ED," the investigators said.
This study was supported in part by the Eleanor and Miles Shore Fellowship Program and the Honjo International Scholarship Foundation. Dr. Hasegawa and his associates reported no financial conflicts of interest.
FROM CIRCULATION: CARDIOVASCULAR QUALITY AND OUTCOMES
Key clinical point: Better preventive care in acute heart failure syndrome patients could cut costly emergency department visits.
Major finding: Most acute heart failure syndrome patients (69%) required only one emergency department visit during the 1-year study, but the remaining 31% were frequent users (overusers) who accounted for more than half of all ED visits and hospitalizations for this condition and for 58% of all near-fatal events.
Data source: A retrospective cohort study of 113,033 adults in California and Florida who presented to an emergency department with acute HF syndrome during a 1-year period.
Disclosures: This study was supported in part by the Eleanor and Miles Shore Fellowship Program and the Honjo International Scholarship Foundation. Dr. Hasegawa and his associates reported no financial conflicts of interest.
Unnecessary cancer screening 'substantial' in U.S.
A substantial proportion of older adults in the United States undergo unnecessary and even harmful screening for colon, prostate, breast, and cervical cancer, contrary to clear guidelines that are widely recognized and well publicized, according to two separate studies published online Aug. 18 in JAMA Internal Medicine.
In the case of colon cancer, most of these unnecessary screenings can be attributed to patients getting rescreened more frequently than at the 10-year intervals recommended and continued screening past the age of 75 years is also a culprit. With the other cancers, the main reason for these unnecessary procedures is continuing screening in patients who have a short life expectancy because of advanced age or irreversible health problems.
In both reports, the investigators emphasized that unnecessary cancer screening is not only inefficient and expensive from a societal perspective but is also harmful for individual patients because it exposes them to invasive procedures and complications, impairs their quality of life, and sometimes leads to downstream overdiagnosis and overtreatment of cancers that would have remained asymptomatic until the patient died of other causes.
In one of the studies, researchers analyzed data from the population-based National Health Interview Survey, which assesses approximately 90,000 Americans each year to provide health information representative of the U.S. population. They focused on 27,404 participants aged 65 years and older who reported on the cancer screening they underwent between 2000 and 2010. A validated mortality index was used to calculate each respondent’s 9-year mortality risk based on factors such as age, sex, smoking status, body mass index, comorbidities, hospitalizations, and functional measures, said Dr. Trevor J. Royce of the departments of radiation oncology and medicine, University of North Carolina at Chapel Hill, and his associates.
They found that contrary to numerous recommendations, "a sizable proportion of the U.S. population who have less than a 9-year life expectancy" underwent screening for cancer, including 55% of men who were screened for prostate cancer, 41% of people screened for colorectal cancer, 38% of women screened for breast cancer, and 31% of women screened for cervical cancer.
Most egregiously, as many as 56% of women who had undergone hysterectomy for benign reasons were still undergoing annual Pap tests to detect cervical cancer, even though most of them no longer had a cervix. And overscreening for prostate cancer was especially common, "possibly because PSA testing is viewed as a simple, safe blood test, with little recognition of the important downstream harms," Dr. Royce and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3895]).
Cancer screening was also common in people whose life expectancy was less than 5 years, or even less than 3 years. Even though the lack of net benefit from cancer screening in such patients "is widely recognized and publicized in clinical practice guidelines, important obstacles exist to reliably applying these guidelines."
Chief among these obstacles is the lack of a simple, reliable tool for assessing life expectancy in clinical practice. In addition, physicians may find it difficult to communicate to patients that they are very likely to die within the next few years, and patients may find it difficult to accept that they have a limited life expectancy or that cancer screening is no longer warranted for them. Physicians’ fear of litigation further contributes to overscreening, Dr. Royce and his associates said.
In the other study, researchers used microsimulation modeling to assess whether screening more intensively than recommended for colorectal cancer would be favorable for individual patients or for society as a whole. They created two hypothetical cohorts of 10 million Medicare beneficiaries at average risk for the disease: the first included patients who had a negative screening colonoscopy at age 55 years and the second included patients who had never been screened for colorectal cancer, said Dr. Frank van Hees of the department of public health, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
The model simulated recommended screening (that is, colonoscopy at ages 65 and 75 years), as well as several shorter screening intervals, screening up to age 85 years, and screening up to age 95 years. It factored into the analyses the sensitivity rates for colonoscopy for adenomas or carcinomas at various stages, age-specific risks for GI and cardiovascular complications requiring hospitalization, and survival rates after a variety of possible clinical diagnoses. "For each scenario of more intensive screening than recommended, we determined the associated increase in colorectal cancer cases prevented, colorectal cancer deaths prevented, life-years gained, life-years with cancer care prevented, colonoscopies performed, and complications experienced," the investigators said.
The balance among benefits, burden, and harm was unfavorable in almost every scenario tested, outside the recommended screening scenario. For example, "when a screening interval of 5 instead of 10 years was applied, the gain in quality of life by preventing additional life-years with colorectal cancer care was exceeded by the loss of quality of life due to additional colonoscopies and additional complications."
Similarly, when colonoscopy was continued to age 85 years instead of ceasing at age 75 years, "the overall loss of quality of life exceeded the associated increase in life-years gained." Harms were even greater when colonoscopy was continued to age 95 years or when the screening interval was reduced to 3 years. "This study provides strong evidence and a clear rationale for clinicians and policy makers to actively discourage this practice," Dr. van Hees and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3889]).
Rather than emphasizing the wastefulness of nonrecommended colorectal cancer screening, stressing that such screening negatively affects patient health is more likely to get both physicians and patients to abandon it. Both physicians and patients should be reminded that "one simple screen" often forces elderly or frail patients with many comorbidities onto a track of continued surveillance, biopsies, and removal of lesions that are unlikely to cause harm, with the attendant complications, the investigators added.
To reduce unneeded cancer screening, clinicians must alter their approach to discussions with older patients, said Dr. Cary P. Gross.
Life expectancy should be addressed, because there is substantial heterogeneity among older persons in life expectancy and comorbidity burden. Informational tools should be developed that can help patients weigh anticipated benefits and harms of screening, given their individual risk. "It will truly be a new era when providers will be evaluated, in part, by their ability to refrain from ordering cancer screening tests for some of their patients," he said.
Dr. Gross is at the Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale University, New Haven, Conn. He reported having ties to FAIR Health, Medtronic, Johnson & Johnson, and 21st Century Oncology. These remarks were taken from his invited commentary accompanying the two reports on cancer screening (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3901]).
To reduce unneeded cancer screening, clinicians must alter their approach to discussions with older patients, said Dr. Cary P. Gross.
Life expectancy should be addressed, because there is substantial heterogeneity among older persons in life expectancy and comorbidity burden. Informational tools should be developed that can help patients weigh anticipated benefits and harms of screening, given their individual risk. "It will truly be a new era when providers will be evaluated, in part, by their ability to refrain from ordering cancer screening tests for some of their patients," he said.
Dr. Gross is at the Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale University, New Haven, Conn. He reported having ties to FAIR Health, Medtronic, Johnson & Johnson, and 21st Century Oncology. These remarks were taken from his invited commentary accompanying the two reports on cancer screening (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3901]).
To reduce unneeded cancer screening, clinicians must alter their approach to discussions with older patients, said Dr. Cary P. Gross.
Life expectancy should be addressed, because there is substantial heterogeneity among older persons in life expectancy and comorbidity burden. Informational tools should be developed that can help patients weigh anticipated benefits and harms of screening, given their individual risk. "It will truly be a new era when providers will be evaluated, in part, by their ability to refrain from ordering cancer screening tests for some of their patients," he said.
Dr. Gross is at the Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale University, New Haven, Conn. He reported having ties to FAIR Health, Medtronic, Johnson & Johnson, and 21st Century Oncology. These remarks were taken from his invited commentary accompanying the two reports on cancer screening (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3901]).
A substantial proportion of older adults in the United States undergo unnecessary and even harmful screening for colon, prostate, breast, and cervical cancer, contrary to clear guidelines that are widely recognized and well publicized, according to two separate studies published online Aug. 18 in JAMA Internal Medicine.
In the case of colon cancer, most of these unnecessary screenings can be attributed to patients getting rescreened more frequently than at the 10-year intervals recommended and continued screening past the age of 75 years is also a culprit. With the other cancers, the main reason for these unnecessary procedures is continuing screening in patients who have a short life expectancy because of advanced age or irreversible health problems.
In both reports, the investigators emphasized that unnecessary cancer screening is not only inefficient and expensive from a societal perspective but is also harmful for individual patients because it exposes them to invasive procedures and complications, impairs their quality of life, and sometimes leads to downstream overdiagnosis and overtreatment of cancers that would have remained asymptomatic until the patient died of other causes.
In one of the studies, researchers analyzed data from the population-based National Health Interview Survey, which assesses approximately 90,000 Americans each year to provide health information representative of the U.S. population. They focused on 27,404 participants aged 65 years and older who reported on the cancer screening they underwent between 2000 and 2010. A validated mortality index was used to calculate each respondent’s 9-year mortality risk based on factors such as age, sex, smoking status, body mass index, comorbidities, hospitalizations, and functional measures, said Dr. Trevor J. Royce of the departments of radiation oncology and medicine, University of North Carolina at Chapel Hill, and his associates.
They found that contrary to numerous recommendations, "a sizable proportion of the U.S. population who have less than a 9-year life expectancy" underwent screening for cancer, including 55% of men who were screened for prostate cancer, 41% of people screened for colorectal cancer, 38% of women screened for breast cancer, and 31% of women screened for cervical cancer.
Most egregiously, as many as 56% of women who had undergone hysterectomy for benign reasons were still undergoing annual Pap tests to detect cervical cancer, even though most of them no longer had a cervix. And overscreening for prostate cancer was especially common, "possibly because PSA testing is viewed as a simple, safe blood test, with little recognition of the important downstream harms," Dr. Royce and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3895]).
Cancer screening was also common in people whose life expectancy was less than 5 years, or even less than 3 years. Even though the lack of net benefit from cancer screening in such patients "is widely recognized and publicized in clinical practice guidelines, important obstacles exist to reliably applying these guidelines."
Chief among these obstacles is the lack of a simple, reliable tool for assessing life expectancy in clinical practice. In addition, physicians may find it difficult to communicate to patients that they are very likely to die within the next few years, and patients may find it difficult to accept that they have a limited life expectancy or that cancer screening is no longer warranted for them. Physicians’ fear of litigation further contributes to overscreening, Dr. Royce and his associates said.
In the other study, researchers used microsimulation modeling to assess whether screening more intensively than recommended for colorectal cancer would be favorable for individual patients or for society as a whole. They created two hypothetical cohorts of 10 million Medicare beneficiaries at average risk for the disease: the first included patients who had a negative screening colonoscopy at age 55 years and the second included patients who had never been screened for colorectal cancer, said Dr. Frank van Hees of the department of public health, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
The model simulated recommended screening (that is, colonoscopy at ages 65 and 75 years), as well as several shorter screening intervals, screening up to age 85 years, and screening up to age 95 years. It factored into the analyses the sensitivity rates for colonoscopy for adenomas or carcinomas at various stages, age-specific risks for GI and cardiovascular complications requiring hospitalization, and survival rates after a variety of possible clinical diagnoses. "For each scenario of more intensive screening than recommended, we determined the associated increase in colorectal cancer cases prevented, colorectal cancer deaths prevented, life-years gained, life-years with cancer care prevented, colonoscopies performed, and complications experienced," the investigators said.
The balance among benefits, burden, and harm was unfavorable in almost every scenario tested, outside the recommended screening scenario. For example, "when a screening interval of 5 instead of 10 years was applied, the gain in quality of life by preventing additional life-years with colorectal cancer care was exceeded by the loss of quality of life due to additional colonoscopies and additional complications."
Similarly, when colonoscopy was continued to age 85 years instead of ceasing at age 75 years, "the overall loss of quality of life exceeded the associated increase in life-years gained." Harms were even greater when colonoscopy was continued to age 95 years or when the screening interval was reduced to 3 years. "This study provides strong evidence and a clear rationale for clinicians and policy makers to actively discourage this practice," Dr. van Hees and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3889]).
Rather than emphasizing the wastefulness of nonrecommended colorectal cancer screening, stressing that such screening negatively affects patient health is more likely to get both physicians and patients to abandon it. Both physicians and patients should be reminded that "one simple screen" often forces elderly or frail patients with many comorbidities onto a track of continued surveillance, biopsies, and removal of lesions that are unlikely to cause harm, with the attendant complications, the investigators added.
A substantial proportion of older adults in the United States undergo unnecessary and even harmful screening for colon, prostate, breast, and cervical cancer, contrary to clear guidelines that are widely recognized and well publicized, according to two separate studies published online Aug. 18 in JAMA Internal Medicine.
In the case of colon cancer, most of these unnecessary screenings can be attributed to patients getting rescreened more frequently than at the 10-year intervals recommended and continued screening past the age of 75 years is also a culprit. With the other cancers, the main reason for these unnecessary procedures is continuing screening in patients who have a short life expectancy because of advanced age or irreversible health problems.
In both reports, the investigators emphasized that unnecessary cancer screening is not only inefficient and expensive from a societal perspective but is also harmful for individual patients because it exposes them to invasive procedures and complications, impairs their quality of life, and sometimes leads to downstream overdiagnosis and overtreatment of cancers that would have remained asymptomatic until the patient died of other causes.
In one of the studies, researchers analyzed data from the population-based National Health Interview Survey, which assesses approximately 90,000 Americans each year to provide health information representative of the U.S. population. They focused on 27,404 participants aged 65 years and older who reported on the cancer screening they underwent between 2000 and 2010. A validated mortality index was used to calculate each respondent’s 9-year mortality risk based on factors such as age, sex, smoking status, body mass index, comorbidities, hospitalizations, and functional measures, said Dr. Trevor J. Royce of the departments of radiation oncology and medicine, University of North Carolina at Chapel Hill, and his associates.
They found that contrary to numerous recommendations, "a sizable proportion of the U.S. population who have less than a 9-year life expectancy" underwent screening for cancer, including 55% of men who were screened for prostate cancer, 41% of people screened for colorectal cancer, 38% of women screened for breast cancer, and 31% of women screened for cervical cancer.
Most egregiously, as many as 56% of women who had undergone hysterectomy for benign reasons were still undergoing annual Pap tests to detect cervical cancer, even though most of them no longer had a cervix. And overscreening for prostate cancer was especially common, "possibly because PSA testing is viewed as a simple, safe blood test, with little recognition of the important downstream harms," Dr. Royce and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3895]).
Cancer screening was also common in people whose life expectancy was less than 5 years, or even less than 3 years. Even though the lack of net benefit from cancer screening in such patients "is widely recognized and publicized in clinical practice guidelines, important obstacles exist to reliably applying these guidelines."
Chief among these obstacles is the lack of a simple, reliable tool for assessing life expectancy in clinical practice. In addition, physicians may find it difficult to communicate to patients that they are very likely to die within the next few years, and patients may find it difficult to accept that they have a limited life expectancy or that cancer screening is no longer warranted for them. Physicians’ fear of litigation further contributes to overscreening, Dr. Royce and his associates said.
In the other study, researchers used microsimulation modeling to assess whether screening more intensively than recommended for colorectal cancer would be favorable for individual patients or for society as a whole. They created two hypothetical cohorts of 10 million Medicare beneficiaries at average risk for the disease: the first included patients who had a negative screening colonoscopy at age 55 years and the second included patients who had never been screened for colorectal cancer, said Dr. Frank van Hees of the department of public health, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
The model simulated recommended screening (that is, colonoscopy at ages 65 and 75 years), as well as several shorter screening intervals, screening up to age 85 years, and screening up to age 95 years. It factored into the analyses the sensitivity rates for colonoscopy for adenomas or carcinomas at various stages, age-specific risks for GI and cardiovascular complications requiring hospitalization, and survival rates after a variety of possible clinical diagnoses. "For each scenario of more intensive screening than recommended, we determined the associated increase in colorectal cancer cases prevented, colorectal cancer deaths prevented, life-years gained, life-years with cancer care prevented, colonoscopies performed, and complications experienced," the investigators said.
The balance among benefits, burden, and harm was unfavorable in almost every scenario tested, outside the recommended screening scenario. For example, "when a screening interval of 5 instead of 10 years was applied, the gain in quality of life by preventing additional life-years with colorectal cancer care was exceeded by the loss of quality of life due to additional colonoscopies and additional complications."
Similarly, when colonoscopy was continued to age 85 years instead of ceasing at age 75 years, "the overall loss of quality of life exceeded the associated increase in life-years gained." Harms were even greater when colonoscopy was continued to age 95 years or when the screening interval was reduced to 3 years. "This study provides strong evidence and a clear rationale for clinicians and policy makers to actively discourage this practice," Dr. van Hees and his associates said (JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3889]).
Rather than emphasizing the wastefulness of nonrecommended colorectal cancer screening, stressing that such screening negatively affects patient health is more likely to get both physicians and patients to abandon it. Both physicians and patients should be reminded that "one simple screen" often forces elderly or frail patients with many comorbidities onto a track of continued surveillance, biopsies, and removal of lesions that are unlikely to cause harm, with the attendant complications, the investigators added.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Cancer screening is not an all-positive tool; life expectancy and complications need to be considered; guidelines have value.
Major finding: 55% of men screened for prostate cancer, 41% of people screened for colorectal cancer, 38% of women screened for breast cancer, and 31% of women screened for cervical cancer were acting contrary to national screening recommendations. For colorectal cancer, the balance among benefits, burden, and harm was unfavorable in almost every scenario tested, outside the recommended screening scenario.
Data source: An analysis of data from the National Health Interview Survey involving screens for prostate, breast, cervical, and colorectal cancer among 27,404 U.S. adults aged 65 years and older between 2000 and 2010 (Dr. Royce), and a simulation modeling study of possible outcomes for hypothetical Medicare beneficiaries at average risk for colorectal cancer who undergo more intensive screening for the disease than recommended (Dr. van Hees).
Disclosures: Dr. Royce’s study was supported in part by the Doris Duke Charitable Foundation; he and his associates reported no ties to industry sources. Dr. van Hees’s study was supported by the National Cancer Institute; he and his associates also reported no ties to industry sources.
Cardiac resynchronization, ICDs benefit all ethnicities with heart failure
Both cardiac resynchronization therapy and implantable cardioverter-defibrillators reduce 2-year mortality in patients with heart failure, regardless of their racial or ethnic backgrounds, according to a report published online Aug. 18 in the Journal of the American College of Cardiology.
Guidelines contain class 1 recommendations for device therapies in the primary prevention of sudden cardiac death among patients with heart failure; cardiac resynchronization therapy (CRT) also has a class 1 recommendation for reducing the risk for events. Because of racial and ethnic disparities in the use of both therapies, as well as an underrepresentation of minorities in clinical trials of these treatments, questions have been raised as to whether black and Hispanic patients gain benefits comparable to those seen in white patients, said Dr. Boback Ziaeian of the division of cardiology at the University of California, Los Angeles, and his associates.
Dr. Ziaeian and his fellow researchers studied this issue using data from the IMPROVE HF registry (Registry to Improve the Use of Evidence-Based HF Therapies in the Outpatient Setting), a prospective observational cohort of 15,177 patients with left ventricular dysfunction and heart failure treated at 167 community and academic cardiology and multispecialty practices. Of 7,748 study participants who were eligible for ICDs/cardiac resynchronization defibrillators, 44% were non-Hispanic whites, 9% were non-Hispanic blacks, and 47% were of other racial/ethnic groups or had no race documented in their records. Of 1,188 who were eligible for cardiac resynchronization pacemakers, 50% were non-Hispanic whites, 8% were non-Hispanic blacks, and 42% were other ethnicities or had no race documented in their records.
At 2-year follow-up, 20.4% of patients who had received CRT or ICD therapy had died as compared with 27.8% of comparable patients who hadn’t received the devices, a 34% reduction in relative risk, the researchers said (J. Amer. Coll. Cardiol. 2014 Aug. 18 [doi:10.1016/j.jacc.2014.05.060]).
The findings "refute any meaningful differences in clinical effectiveness as a function of race/ethnicity for either ICD or CRT-D (implantable cardioverter defibrillator with bradycardia pacing capabilities) therapy ... [and] reinforce current class 1 recommendations from the American College of Cardiology/American Heart Association HF guidelines that selected HF patients without racial/ethnic differentiation should, in the absence of specific evidence to treat otherwise, have clinical screening and therapy in a manner identical to that provided to the broader HF population," the researchers concluded.
The study was supported by Medtronic. Dr. Ziaeian and his associates reported ties to numerous industry sources.
Although this study by Ziaeian et al. was one of the largest trials to date to address the issue of ICD/CRT therapies with regard to race/ethnicity, the number of racial/ethnic minorities was still relatively small. The study was only modestly powered to detect interactions indicating that treatment benefits may vary according to the patient’s background.
Importantly, the ICD/CRT-D cohort only had 75% power to detect a device-race interaction, the ICD-only cohort only had 41% power to detect a device-race interaction, and the cardiac resynchronization pacemaker/CRT-D cohort only had 15% power to detect a device-race interaction. Nevertheless, the focus should now be on improving care delivery models to eliminate performance gaps and ensure equal care for all Americans.
Dr. Sean P. Pinney is at the Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai Hospital, New York. He reported receiving consulting fees and honoraria from CareDx and Thoratec. His remarks were taken from an editorial accompanying Dr. Ziaeian’s report (J. Amer. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.07.008]).
Although this study by Ziaeian et al. was one of the largest trials to date to address the issue of ICD/CRT therapies with regard to race/ethnicity, the number of racial/ethnic minorities was still relatively small. The study was only modestly powered to detect interactions indicating that treatment benefits may vary according to the patient’s background.
Importantly, the ICD/CRT-D cohort only had 75% power to detect a device-race interaction, the ICD-only cohort only had 41% power to detect a device-race interaction, and the cardiac resynchronization pacemaker/CRT-D cohort only had 15% power to detect a device-race interaction. Nevertheless, the focus should now be on improving care delivery models to eliminate performance gaps and ensure equal care for all Americans.
Dr. Sean P. Pinney is at the Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai Hospital, New York. He reported receiving consulting fees and honoraria from CareDx and Thoratec. His remarks were taken from an editorial accompanying Dr. Ziaeian’s report (J. Amer. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.07.008]).
Although this study by Ziaeian et al. was one of the largest trials to date to address the issue of ICD/CRT therapies with regard to race/ethnicity, the number of racial/ethnic minorities was still relatively small. The study was only modestly powered to detect interactions indicating that treatment benefits may vary according to the patient’s background.
Importantly, the ICD/CRT-D cohort only had 75% power to detect a device-race interaction, the ICD-only cohort only had 41% power to detect a device-race interaction, and the cardiac resynchronization pacemaker/CRT-D cohort only had 15% power to detect a device-race interaction. Nevertheless, the focus should now be on improving care delivery models to eliminate performance gaps and ensure equal care for all Americans.
Dr. Sean P. Pinney is at the Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai Hospital, New York. He reported receiving consulting fees and honoraria from CareDx and Thoratec. His remarks were taken from an editorial accompanying Dr. Ziaeian’s report (J. Amer. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.07.008]).
Both cardiac resynchronization therapy and implantable cardioverter-defibrillators reduce 2-year mortality in patients with heart failure, regardless of their racial or ethnic backgrounds, according to a report published online Aug. 18 in the Journal of the American College of Cardiology.
Guidelines contain class 1 recommendations for device therapies in the primary prevention of sudden cardiac death among patients with heart failure; cardiac resynchronization therapy (CRT) also has a class 1 recommendation for reducing the risk for events. Because of racial and ethnic disparities in the use of both therapies, as well as an underrepresentation of minorities in clinical trials of these treatments, questions have been raised as to whether black and Hispanic patients gain benefits comparable to those seen in white patients, said Dr. Boback Ziaeian of the division of cardiology at the University of California, Los Angeles, and his associates.
Dr. Ziaeian and his fellow researchers studied this issue using data from the IMPROVE HF registry (Registry to Improve the Use of Evidence-Based HF Therapies in the Outpatient Setting), a prospective observational cohort of 15,177 patients with left ventricular dysfunction and heart failure treated at 167 community and academic cardiology and multispecialty practices. Of 7,748 study participants who were eligible for ICDs/cardiac resynchronization defibrillators, 44% were non-Hispanic whites, 9% were non-Hispanic blacks, and 47% were of other racial/ethnic groups or had no race documented in their records. Of 1,188 who were eligible for cardiac resynchronization pacemakers, 50% were non-Hispanic whites, 8% were non-Hispanic blacks, and 42% were other ethnicities or had no race documented in their records.
At 2-year follow-up, 20.4% of patients who had received CRT or ICD therapy had died as compared with 27.8% of comparable patients who hadn’t received the devices, a 34% reduction in relative risk, the researchers said (J. Amer. Coll. Cardiol. 2014 Aug. 18 [doi:10.1016/j.jacc.2014.05.060]).
The findings "refute any meaningful differences in clinical effectiveness as a function of race/ethnicity for either ICD or CRT-D (implantable cardioverter defibrillator with bradycardia pacing capabilities) therapy ... [and] reinforce current class 1 recommendations from the American College of Cardiology/American Heart Association HF guidelines that selected HF patients without racial/ethnic differentiation should, in the absence of specific evidence to treat otherwise, have clinical screening and therapy in a manner identical to that provided to the broader HF population," the researchers concluded.
The study was supported by Medtronic. Dr. Ziaeian and his associates reported ties to numerous industry sources.
Both cardiac resynchronization therapy and implantable cardioverter-defibrillators reduce 2-year mortality in patients with heart failure, regardless of their racial or ethnic backgrounds, according to a report published online Aug. 18 in the Journal of the American College of Cardiology.
Guidelines contain class 1 recommendations for device therapies in the primary prevention of sudden cardiac death among patients with heart failure; cardiac resynchronization therapy (CRT) also has a class 1 recommendation for reducing the risk for events. Because of racial and ethnic disparities in the use of both therapies, as well as an underrepresentation of minorities in clinical trials of these treatments, questions have been raised as to whether black and Hispanic patients gain benefits comparable to those seen in white patients, said Dr. Boback Ziaeian of the division of cardiology at the University of California, Los Angeles, and his associates.
Dr. Ziaeian and his fellow researchers studied this issue using data from the IMPROVE HF registry (Registry to Improve the Use of Evidence-Based HF Therapies in the Outpatient Setting), a prospective observational cohort of 15,177 patients with left ventricular dysfunction and heart failure treated at 167 community and academic cardiology and multispecialty practices. Of 7,748 study participants who were eligible for ICDs/cardiac resynchronization defibrillators, 44% were non-Hispanic whites, 9% were non-Hispanic blacks, and 47% were of other racial/ethnic groups or had no race documented in their records. Of 1,188 who were eligible for cardiac resynchronization pacemakers, 50% were non-Hispanic whites, 8% were non-Hispanic blacks, and 42% were other ethnicities or had no race documented in their records.
At 2-year follow-up, 20.4% of patients who had received CRT or ICD therapy had died as compared with 27.8% of comparable patients who hadn’t received the devices, a 34% reduction in relative risk, the researchers said (J. Amer. Coll. Cardiol. 2014 Aug. 18 [doi:10.1016/j.jacc.2014.05.060]).
The findings "refute any meaningful differences in clinical effectiveness as a function of race/ethnicity for either ICD or CRT-D (implantable cardioverter defibrillator with bradycardia pacing capabilities) therapy ... [and] reinforce current class 1 recommendations from the American College of Cardiology/American Heart Association HF guidelines that selected HF patients without racial/ethnic differentiation should, in the absence of specific evidence to treat otherwise, have clinical screening and therapy in a manner identical to that provided to the broader HF population," the researchers concluded.
The study was supported by Medtronic. Dr. Ziaeian and his associates reported ties to numerous industry sources.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Ethnicity should not influence which heart failure patients are candidates for device therapy.
Major finding: At 2-year follow-up, the mortality rate was 20.4% for patients who had received CRT or ICD therapy as recommended and 27.8% for those who hadn’t received the devices as recommended – a 34% difference in relative risk irrespective of ethnicity.
Data source: An analysis of the medical records of 8,936 heart failure patients who were eligible for either CRT or ICD therapy and were followed for 2 years.
Disclosures: This study was supported by Medtronic. Dr. Ziaeian and his associates reported ties to numerous industry sources.
Sodium Controversy: More Fuel for the Fire
Three large international studies addressing sodium intake’s effect on blood pressure and on cardiovascular and mortality outcomes are not likely to quell the controversy surrounding this issue. Rather, since the findings of one study directly oppose those of the other two, the results promise to fan the flames a bit higher.
All three studies were reported online August 14 in the New England Journal of Medicine.
Sodium and blood pressure: PURE
The first report concerned a substudy of data from the Prospective Urban Rural Epidemiology (PURE) study involving 102,216 adults aged 35-70 years residing in 667 communities in 18 low-, middle-, and high-income countries worldwide. Urinary sodium and potassium levels were used as surrogates for dietary intake of these elements, and these excretion levels were correlated with the participants’ blood pressure levels, said Andrew Mente, Ph.D., of the Population Health Research Institute, Hamilton (Ont.) Health Services, McMaster University, and his associates.
Current guidelines recommend a maximum sodium intake of 1.5-2.4 g/day, depending on the country. Only 0.6% of the study population achieved the lowest level of 1.5 g/day, the level recommended in the United States, and only 10% achieved less than 3 g/day. The largest segment of the study population, 46%, had a sodium excretion of 3-5 g/day, and the next largest segment, 44%, had a sodium excretion of more than 5 g/day.
"This suggests that, at present, human consumption of extremely low amounts of sodium for prolonged periods is rare," the investigators noted.
The investigators found, after multivariate adjustment, that for each 1-g increment in sodium excretion, there was an increment of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure (P less than .001 for both) for all areas of the globe.
However, this correlation was nonlinear. The association between sodium and blood pressure was weak in the largest subset of participants who had an excretion of 3-5 g/day, and was nonsignificant in those who had an excretion of less than 3 g/day.
The association between sodium intake and blood pressure was stronger in people who had an excretion of more than 5 g/day and in those who already had hypertension at baseline. It also increased with increasing patient age.
Taken together, these findings indicate that sodium’s effect on blood pressure is nonuniform and depends on the background diet of the population as well as the individual’s age and hypertension status, Dr. Mente and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:601-11 [doi:10.1056/NEJMoa1311989]).
Sodium and cardiovascular mortality: PURE
The second report also was a substudy of the PURE study, this time headed by Dr. Martin O’Donnell of the Population Health Institute and McMaster University. The researchers performed a prospective cohort study involving 101,945 PURE participants to assess the association between baseline urinary sodium and potassium excretion, again as a surrogate for intake, with mortality and incident cardiovascular (CV) events during 3.7 years of follow-up.
The primary composite outcome of death or a major CV event occurred in 3,317 participants (3.3%). The mean 24-hour sodium excretion was 4.9 g.
Surprisingly, the lowest risk of death and CV events was seen not in people with the recommended levels of sodium excretion but in those whose sodium excretion was much higher, at 3-6 g/day. Risks actually increased at levels of sodium excretion that were lower than 3 g/day, as is recommended, as well as at levels that were higher than 6 g/day. Moreover, the association between high sodium excretion and high CV and mortality risk was significant only among adults who already had hypertension at baseline.
"The projected benefits of low sodium intake ... are derived from models ... that assume a linear relationship between sodium intake and blood pressure and between blood pressure and cardiovascular events. Implicit in these guidelines is the assumption that there is no unsafe lower limit of sodium intake," Dr. O’Donnell and his associates wrote (N. Engl. J. Med. 2014 Aug. 14;371:612-23 [doi:10.1056/NEJMoa131889]).
The findings from both of these PURE studies call those assumptions into question.
Sodium and cardiovascular mortality: NUTRICODE
The third report was a review of the literature regarding sodium intake’s effect on CV mortality worldwide; the gathered data then served as the basis for a complex statistical model that estimated how many deaths could be attributed to sodium consumption in excess of a reference level of 2.0 g/day. This study was performed by the Global Burden of Diseases, Nutrition, and Chronic Diseases Expert Group (NUTRICODE) and was headed by Dr. Dariush Mozaffarian, a cardiologist and epidemiologist with Tufts University and the Harvard School of Public Health, both in Boston.
These investigators quantified sodium intake in 66 countries (accounting for 74% of adults throughout the world) by age, sex, and country of residence, and correlated these data first with findings from their meta-analysis of 107 randomized trials of interventions to curb sodium intake and then with the results of two large international trials linking the effects of various blood pressure levels on CV mortality.
They estimated that the mean level of sodium intake worldwide is 3.95 g/day and that those mean levels varied by geographic region from a low of 2.18 g to a high of 5.51 g. "Overall, 181 of 187 countries – 99.2% of the adult population of the world – had estimated mean levels of sodium intake exceeding the World Health Organization recommendation of 2.0 g/day," Dr. Mozaffarian and his associates said.
Contrary to the findings of the two PURE analyses, these data showed "strong evidence of a linear dose-response relationship" between sodium intake and blood pressure, such that each reduction of 2.30 g/day of sodium was significantly linked with a reduction of 3.82 mm Hg in systolic blood pressure, as well as a direct correlation between increasing blood pressure and increasing CV mortality.
Extrapolating from these data, "we found that 1.65 million deaths from CV causes worldwide in 2010 were attributable to sodium consumption above the reference level" of 2 g/day. "Globally, 40.4% of these deaths occurred prematurely, i.e. in persons younger than 70 years of age," Dr. Mozaffarian and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:624-34 [doi:10.1056/NEJMoa1304127]).
"In sum, approximately 1 of every 10 deaths from CV causes worldwide and nearly 1 of every 5 premature deaths from CV causes were attributed to sodium consumption above the reference level," they said.
In an editorial accompanying this report, Dr. Suzanne Oparil said, "The NUTRICODE investigators should be applauded for a herculean effort in synthesizing a large body of data regarding the potential harm of excess salt consumption" (N. Engl. J. Med. 2014 Aug. 14;371:677-9 [doi:10.1056/NEJMe1407695]).
"However, given the numerous assumptions necessitated by the lack of high-quality data [in the literature], caution should be taken in interpreting the findings of this study," said Dr. Oparil of the vascular biology and hypertension program, University of Alabama at Birmingham.
The PURE studies were supported by the Heart and Stroke Foundation of Ontario, the Population Health Research Institute, the Canadian Institutes of Health Research, several pharmaceutical companies, and various national or local organizations in 18 participating countries. These funders played no role in the design or conduct of the studies, in collection or analysis of data, or in preparing the manuscript. Dr. O’Donnell reported ties to Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to Sanofi-Aventis, AstraZeneca, and Cadila. The NUTRICODE study was funded by the Bill and Melinda Gates Foundation.
Three large international studies addressing sodium intake’s effect on blood pressure and on cardiovascular and mortality outcomes are not likely to quell the controversy surrounding this issue. Rather, since the findings of one study directly oppose those of the other two, the results promise to fan the flames a bit higher.
All three studies were reported online August 14 in the New England Journal of Medicine.
Sodium and blood pressure: PURE
The first report concerned a substudy of data from the Prospective Urban Rural Epidemiology (PURE) study involving 102,216 adults aged 35-70 years residing in 667 communities in 18 low-, middle-, and high-income countries worldwide. Urinary sodium and potassium levels were used as surrogates for dietary intake of these elements, and these excretion levels were correlated with the participants’ blood pressure levels, said Andrew Mente, Ph.D., of the Population Health Research Institute, Hamilton (Ont.) Health Services, McMaster University, and his associates.
Current guidelines recommend a maximum sodium intake of 1.5-2.4 g/day, depending on the country. Only 0.6% of the study population achieved the lowest level of 1.5 g/day, the level recommended in the United States, and only 10% achieved less than 3 g/day. The largest segment of the study population, 46%, had a sodium excretion of 3-5 g/day, and the next largest segment, 44%, had a sodium excretion of more than 5 g/day.
"This suggests that, at present, human consumption of extremely low amounts of sodium for prolonged periods is rare," the investigators noted.
The investigators found, after multivariate adjustment, that for each 1-g increment in sodium excretion, there was an increment of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure (P less than .001 for both) for all areas of the globe.
However, this correlation was nonlinear. The association between sodium and blood pressure was weak in the largest subset of participants who had an excretion of 3-5 g/day, and was nonsignificant in those who had an excretion of less than 3 g/day.
The association between sodium intake and blood pressure was stronger in people who had an excretion of more than 5 g/day and in those who already had hypertension at baseline. It also increased with increasing patient age.
Taken together, these findings indicate that sodium’s effect on blood pressure is nonuniform and depends on the background diet of the population as well as the individual’s age and hypertension status, Dr. Mente and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:601-11 [doi:10.1056/NEJMoa1311989]).
Sodium and cardiovascular mortality: PURE
The second report also was a substudy of the PURE study, this time headed by Dr. Martin O’Donnell of the Population Health Institute and McMaster University. The researchers performed a prospective cohort study involving 101,945 PURE participants to assess the association between baseline urinary sodium and potassium excretion, again as a surrogate for intake, with mortality and incident cardiovascular (CV) events during 3.7 years of follow-up.
The primary composite outcome of death or a major CV event occurred in 3,317 participants (3.3%). The mean 24-hour sodium excretion was 4.9 g.
Surprisingly, the lowest risk of death and CV events was seen not in people with the recommended levels of sodium excretion but in those whose sodium excretion was much higher, at 3-6 g/day. Risks actually increased at levels of sodium excretion that were lower than 3 g/day, as is recommended, as well as at levels that were higher than 6 g/day. Moreover, the association between high sodium excretion and high CV and mortality risk was significant only among adults who already had hypertension at baseline.
"The projected benefits of low sodium intake ... are derived from models ... that assume a linear relationship between sodium intake and blood pressure and between blood pressure and cardiovascular events. Implicit in these guidelines is the assumption that there is no unsafe lower limit of sodium intake," Dr. O’Donnell and his associates wrote (N. Engl. J. Med. 2014 Aug. 14;371:612-23 [doi:10.1056/NEJMoa131889]).
The findings from both of these PURE studies call those assumptions into question.
Sodium and cardiovascular mortality: NUTRICODE
The third report was a review of the literature regarding sodium intake’s effect on CV mortality worldwide; the gathered data then served as the basis for a complex statistical model that estimated how many deaths could be attributed to sodium consumption in excess of a reference level of 2.0 g/day. This study was performed by the Global Burden of Diseases, Nutrition, and Chronic Diseases Expert Group (NUTRICODE) and was headed by Dr. Dariush Mozaffarian, a cardiologist and epidemiologist with Tufts University and the Harvard School of Public Health, both in Boston.
These investigators quantified sodium intake in 66 countries (accounting for 74% of adults throughout the world) by age, sex, and country of residence, and correlated these data first with findings from their meta-analysis of 107 randomized trials of interventions to curb sodium intake and then with the results of two large international trials linking the effects of various blood pressure levels on CV mortality.
They estimated that the mean level of sodium intake worldwide is 3.95 g/day and that those mean levels varied by geographic region from a low of 2.18 g to a high of 5.51 g. "Overall, 181 of 187 countries – 99.2% of the adult population of the world – had estimated mean levels of sodium intake exceeding the World Health Organization recommendation of 2.0 g/day," Dr. Mozaffarian and his associates said.
Contrary to the findings of the two PURE analyses, these data showed "strong evidence of a linear dose-response relationship" between sodium intake and blood pressure, such that each reduction of 2.30 g/day of sodium was significantly linked with a reduction of 3.82 mm Hg in systolic blood pressure, as well as a direct correlation between increasing blood pressure and increasing CV mortality.
Extrapolating from these data, "we found that 1.65 million deaths from CV causes worldwide in 2010 were attributable to sodium consumption above the reference level" of 2 g/day. "Globally, 40.4% of these deaths occurred prematurely, i.e. in persons younger than 70 years of age," Dr. Mozaffarian and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:624-34 [doi:10.1056/NEJMoa1304127]).
"In sum, approximately 1 of every 10 deaths from CV causes worldwide and nearly 1 of every 5 premature deaths from CV causes were attributed to sodium consumption above the reference level," they said.
In an editorial accompanying this report, Dr. Suzanne Oparil said, "The NUTRICODE investigators should be applauded for a herculean effort in synthesizing a large body of data regarding the potential harm of excess salt consumption" (N. Engl. J. Med. 2014 Aug. 14;371:677-9 [doi:10.1056/NEJMe1407695]).
"However, given the numerous assumptions necessitated by the lack of high-quality data [in the literature], caution should be taken in interpreting the findings of this study," said Dr. Oparil of the vascular biology and hypertension program, University of Alabama at Birmingham.
The PURE studies were supported by the Heart and Stroke Foundation of Ontario, the Population Health Research Institute, the Canadian Institutes of Health Research, several pharmaceutical companies, and various national or local organizations in 18 participating countries. These funders played no role in the design or conduct of the studies, in collection or analysis of data, or in preparing the manuscript. Dr. O’Donnell reported ties to Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to Sanofi-Aventis, AstraZeneca, and Cadila. The NUTRICODE study was funded by the Bill and Melinda Gates Foundation.
Three large international studies addressing sodium intake’s effect on blood pressure and on cardiovascular and mortality outcomes are not likely to quell the controversy surrounding this issue. Rather, since the findings of one study directly oppose those of the other two, the results promise to fan the flames a bit higher.
All three studies were reported online August 14 in the New England Journal of Medicine.
Sodium and blood pressure: PURE
The first report concerned a substudy of data from the Prospective Urban Rural Epidemiology (PURE) study involving 102,216 adults aged 35-70 years residing in 667 communities in 18 low-, middle-, and high-income countries worldwide. Urinary sodium and potassium levels were used as surrogates for dietary intake of these elements, and these excretion levels were correlated with the participants’ blood pressure levels, said Andrew Mente, Ph.D., of the Population Health Research Institute, Hamilton (Ont.) Health Services, McMaster University, and his associates.
Current guidelines recommend a maximum sodium intake of 1.5-2.4 g/day, depending on the country. Only 0.6% of the study population achieved the lowest level of 1.5 g/day, the level recommended in the United States, and only 10% achieved less than 3 g/day. The largest segment of the study population, 46%, had a sodium excretion of 3-5 g/day, and the next largest segment, 44%, had a sodium excretion of more than 5 g/day.
"This suggests that, at present, human consumption of extremely low amounts of sodium for prolonged periods is rare," the investigators noted.
The investigators found, after multivariate adjustment, that for each 1-g increment in sodium excretion, there was an increment of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure (P less than .001 for both) for all areas of the globe.
However, this correlation was nonlinear. The association between sodium and blood pressure was weak in the largest subset of participants who had an excretion of 3-5 g/day, and was nonsignificant in those who had an excretion of less than 3 g/day.
The association between sodium intake and blood pressure was stronger in people who had an excretion of more than 5 g/day and in those who already had hypertension at baseline. It also increased with increasing patient age.
Taken together, these findings indicate that sodium’s effect on blood pressure is nonuniform and depends on the background diet of the population as well as the individual’s age and hypertension status, Dr. Mente and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:601-11 [doi:10.1056/NEJMoa1311989]).
Sodium and cardiovascular mortality: PURE
The second report also was a substudy of the PURE study, this time headed by Dr. Martin O’Donnell of the Population Health Institute and McMaster University. The researchers performed a prospective cohort study involving 101,945 PURE participants to assess the association between baseline urinary sodium and potassium excretion, again as a surrogate for intake, with mortality and incident cardiovascular (CV) events during 3.7 years of follow-up.
The primary composite outcome of death or a major CV event occurred in 3,317 participants (3.3%). The mean 24-hour sodium excretion was 4.9 g.
Surprisingly, the lowest risk of death and CV events was seen not in people with the recommended levels of sodium excretion but in those whose sodium excretion was much higher, at 3-6 g/day. Risks actually increased at levels of sodium excretion that were lower than 3 g/day, as is recommended, as well as at levels that were higher than 6 g/day. Moreover, the association between high sodium excretion and high CV and mortality risk was significant only among adults who already had hypertension at baseline.
"The projected benefits of low sodium intake ... are derived from models ... that assume a linear relationship between sodium intake and blood pressure and between blood pressure and cardiovascular events. Implicit in these guidelines is the assumption that there is no unsafe lower limit of sodium intake," Dr. O’Donnell and his associates wrote (N. Engl. J. Med. 2014 Aug. 14;371:612-23 [doi:10.1056/NEJMoa131889]).
The findings from both of these PURE studies call those assumptions into question.
Sodium and cardiovascular mortality: NUTRICODE
The third report was a review of the literature regarding sodium intake’s effect on CV mortality worldwide; the gathered data then served as the basis for a complex statistical model that estimated how many deaths could be attributed to sodium consumption in excess of a reference level of 2.0 g/day. This study was performed by the Global Burden of Diseases, Nutrition, and Chronic Diseases Expert Group (NUTRICODE) and was headed by Dr. Dariush Mozaffarian, a cardiologist and epidemiologist with Tufts University and the Harvard School of Public Health, both in Boston.
These investigators quantified sodium intake in 66 countries (accounting for 74% of adults throughout the world) by age, sex, and country of residence, and correlated these data first with findings from their meta-analysis of 107 randomized trials of interventions to curb sodium intake and then with the results of two large international trials linking the effects of various blood pressure levels on CV mortality.
They estimated that the mean level of sodium intake worldwide is 3.95 g/day and that those mean levels varied by geographic region from a low of 2.18 g to a high of 5.51 g. "Overall, 181 of 187 countries – 99.2% of the adult population of the world – had estimated mean levels of sodium intake exceeding the World Health Organization recommendation of 2.0 g/day," Dr. Mozaffarian and his associates said.
Contrary to the findings of the two PURE analyses, these data showed "strong evidence of a linear dose-response relationship" between sodium intake and blood pressure, such that each reduction of 2.30 g/day of sodium was significantly linked with a reduction of 3.82 mm Hg in systolic blood pressure, as well as a direct correlation between increasing blood pressure and increasing CV mortality.
Extrapolating from these data, "we found that 1.65 million deaths from CV causes worldwide in 2010 were attributable to sodium consumption above the reference level" of 2 g/day. "Globally, 40.4% of these deaths occurred prematurely, i.e. in persons younger than 70 years of age," Dr. Mozaffarian and his associates said (N. Engl. J. Med. 2014 Aug. 14;371:624-34 [doi:10.1056/NEJMoa1304127]).
"In sum, approximately 1 of every 10 deaths from CV causes worldwide and nearly 1 of every 5 premature deaths from CV causes were attributed to sodium consumption above the reference level," they said.
In an editorial accompanying this report, Dr. Suzanne Oparil said, "The NUTRICODE investigators should be applauded for a herculean effort in synthesizing a large body of data regarding the potential harm of excess salt consumption" (N. Engl. J. Med. 2014 Aug. 14;371:677-9 [doi:10.1056/NEJMe1407695]).
"However, given the numerous assumptions necessitated by the lack of high-quality data [in the literature], caution should be taken in interpreting the findings of this study," said Dr. Oparil of the vascular biology and hypertension program, University of Alabama at Birmingham.
The PURE studies were supported by the Heart and Stroke Foundation of Ontario, the Population Health Research Institute, the Canadian Institutes of Health Research, several pharmaceutical companies, and various national or local organizations in 18 participating countries. These funders played no role in the design or conduct of the studies, in collection or analysis of data, or in preparing the manuscript. Dr. O’Donnell reported ties to Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to Sanofi-Aventis, AstraZeneca, and Cadila. The NUTRICODE study was funded by the Bill and Melinda Gates Foundation.
High-dose flu vaccine more effective for elderly
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
The high-dose version of the trivalent inactivated influenza vaccine induced higher antibody responses and provided significantly improved protection against the disease in patients aged 65 years and older participating in an industry-sponsored phase III-IV randomized, controlled trial, which was reported online Aug. 14 in the New England Journal of Medicine.
The standard-dose vaccine is less effective in older adults, with an absolute efficacy of approximately 50%, than in adults younger than age 65 years. In comparison, given the findings of this large clinical trial, "the absolute efficacy of the high-dose vaccine would be estimated at 62%, a level of protection similar to that seen with standard-dose vaccines in younger adults," said Dr. Carlos A. DiazGranados of Sanofi Pasteur, Swiftwater, Pa., and his associates.
The high-dose trivalent inactivated vaccine, IIV3-HD (Fluzone High Dose), was licensed for use in the United States in 2009, with a requirement to show clinical benefits. This trial was designed to demonstrate those benefits by comparing its efficacy against that of the standard-dose vaccine (Fluzone) in the elderly.
A total of 31,989 adults aged 65 years and older participated in the double-blind trial at 126 medical centers in the United States and Canada during a 20-month period (two flu seasons). They were randomly assigned to receive a single intramuscular dose of either the standard-dose vaccine, which contains 15 mcg of hemagglutinin/strain (15,998 patients), or the high-dose vaccine, which contains 60 mcg of hemagglutinin/strain (15,991 patients).
Blood samples collected from a subset of approximately one-third of the study participants showed that antibody levels for all three influenza strains were significantly higher in members of the high-dose group than in those in the low-dose group at 28 days after vaccination.
The primary endpoint of the trial was the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination. This occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group. Therefore, the efficacy of IIV3-HD relative to the standard-dose vaccine was 24.2%, which met the study criterion for superiority, the researchers stated.
This level of efficacy "indicates that about one-quarter of all breakthrough influenza illnesses could be prevented if IIV3-HD were used" instead of the standard-dose vaccine in this age group, Dr. DiazGranados and his associates said (N. Engl. J. Med. 2014 Aug. 14 [doi:10.1056/NEJMoa1315727]).
In addition, rates of pneumonia, cardiorespiratory conditions, hospitalizations, nonroutine medical office visits, and medication use were lower in the high-dose than in the low-dose group. This suggests that the clinical benefits of IIV3-HD will translate into public health benefits, they said.
The rate of serious adverse events was slightly higher with the standard-dose vaccine (9.0%) than with the high-dose vaccine (8.3%). The rate of withdrawal from the study because of adverse events was identical between the two groups at 0.6%, and none of those events were considered to be related to vaccination.
Three patients who received the high-dose vaccine had serious adverse events considered to be related to vaccination: one developed cranial-nerve VI palsy the day after the injection; one developed hypovolemic shock from diarrhea that started the day after the injection; and one developed acute disseminated encephalomyelitis that began 117 days after vaccination. All of these events resolved over time.
This trial was funded by Sanofi-Pasteur, maker of IIV3-HD, which also was involved in study design and monitoring, data management, and statistical analysis.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: In patients over age 65 years, high-dose flu vaccine was more protective than was standard dose vaccine.
Major finding: The primary endpoint of the trial – the development of influenzalike illness, together with laboratory-confirmed influenza caused by any viral type, at least 14 days after vaccination – occurred in 301 patients (1.9%) in the standard-dose group, compared with 228 patients (1.4%) in the high-dose group.
Data source: A multicenter double-blind randomized phase III-IV clinical trial involving 31,989 adults aged 65 years and older who received either the standard-dose or a high-dose trivalent influenza vaccination during the course of two flu seasons.
Disclosures: This trial was funded by Sanofi-Pasteur, maker of IIV3-HD (Fluzone High Dose), which also was involved in study design and monitoring, data management, and statistical analysis.