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Model Suggests Avoiding Statins After Intracerebral Hemorrhage
Clinicians should consider avoiding statins in patients with intracerebral hemorrhage who are at high risk of recurrence because the risks of the drugs appear to outweigh their benefits, according to a report published online Jan. 10 in Archives of Neurology.
After an increased incidence of intracerebral hemorrhage (ICH) was reported among subjects in a randomized clinical trial that evaluated statin therapy, Dr. M. Brandon Westover of the department of neurology at Massachusetts General Hospital and Harvard Medical School, Boston, and his associates developed a mathematical decision analysis model to assess the "common dilemma facing physicians of patients with a history of prior ICH and indications for statin therapy: Under what clinical circumstances should statin therapy be avoided because of risk of recurrent ICH?"
Their analysis indicates that "for lobar ICH in particular, which has a substantially higher recurrence rate than does deep ICH, statin therapy is predicted to increase the baseline annual probability of recurrence from approximately 14% to approximately 22%, offsetting the cardiovascular benefits for both primary and secondary CV prevention."
The model simulated the effects of statin therapy on quality-adjusted life expectancy for a hypothetical 65-year-old male patient under different clinical circumstances. It incorporated published data on risks and benefits.
In the scenario of a patient with a lobar ICH and no prior history of ischemic cerebrovascular or cardiac events, statin therapy yielded 4.6 quality-adjusted life years (QALYs), whereas avoiding statin therapy yielded 6.8 QALYs. Avoiding statins also proved advantageous in all other primary prevention scenarios run by the simulation model.
Similarly, avoiding statins was the preferable course of action in several secondary prevention scenarios featuring a patient with lobar ICH. "These results indicate that the risk of ICH on statin therapy is not offset by the secondary prevention benefits, even if the cardiovascular risks are artificially forced to be extremely high," Dr. Westover and his colleagues wrote.
The model indicated that the risks of statin therapy were substantially lower in hypothetical patients with deep ICH, but still conveyed a net loss of QALYs when used for either primary or secondary prevention.
"Using the base-case assumptions and measuring over a single year of follow-up, primary prevention with statin therapy is projected to prevent fewer than two deaths from either MI or ischemic stroke per 1,000 patients per year, at the expense of causing 18 lobar ICHs (in patients with prior lobar ICH) or 3 deep ICHs (in patients with prior deep ICH) per 1,000 patients per year.
"From the perspective of disability and resulting loss of quality of life, each year of primary prevention with statin treatment saves 2.6 QALYs from myocardial infarction or 2.2 QALYs from ischemic stroke per 1,000 patients per year, at the expense of 58.6 QALYs for lobar ICH or 9 QALYs for deep ICH," they noted (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.356]).
The mechanism by which statins may amplify the risk of hemorrhagic stroke is still unclear, but the drugs are known to have pleiotropic effects independent of their effects on cholesterol levels, which could in turn convey antithrombotic or fibrinolytic changes.
"Mathematical decision analysis of the available data suggests that, because of the high risk of recurrent ICH in survivors of prior hemorrhagic stroke, even a small amplification of this risk by use of statins suffices to recommend that they should be avoided after ICH. In the absence of data from a randomized clinical trial (ideally comparing various agents and doses), the current model provides some guidance for clinicians facing this difficult decision," the investigators said.
The study was supported by the National Institutes of Health. No financial conflicts of interest were reported.
Dr. Larry B. Goldstein |
The conclusion of this decision analysis is generally consistent with the data amassed to date: The risks of statin therapy likely outweigh any potential benefit in patients with recent brain hemorrhage, and the drugs should be avoided in this setting, according to Dr. Larry B. Goldstein.
However, any decision analysis is limited by the data on which its assumptions are based. And the clinical trial data concerning risk of recurrent bleeding in this patient population are very sparse.
In particular, the small number of recurrent strokes in different studies of the issue is limiting. Some studies did not distinguish between lobar intracerebral hemorrhage and deep ICH, and as Dr. Westover and his colleagues point out, the risk of ICH recurrence is quite different between these two entities. Some studies were only exploratory, and their results apply only to patients taking very specific statin doses under specific clinical conditions, he noted.
Dr. Goldstein is director of the stroke center at Duke University, Durham, N.C. He is on the steering committee of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial, which is sponsored by Pfizer. He is also a consultant for Pfizer and Merck. These comments were taken from his editorial accompanying Dr. Westover’s report (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.349]).
Dr. Larry B. Goldstein |
The conclusion of this decision analysis is generally consistent with the data amassed to date: The risks of statin therapy likely outweigh any potential benefit in patients with recent brain hemorrhage, and the drugs should be avoided in this setting, according to Dr. Larry B. Goldstein.
However, any decision analysis is limited by the data on which its assumptions are based. And the clinical trial data concerning risk of recurrent bleeding in this patient population are very sparse.
In particular, the small number of recurrent strokes in different studies of the issue is limiting. Some studies did not distinguish between lobar intracerebral hemorrhage and deep ICH, and as Dr. Westover and his colleagues point out, the risk of ICH recurrence is quite different between these two entities. Some studies were only exploratory, and their results apply only to patients taking very specific statin doses under specific clinical conditions, he noted.
Dr. Goldstein is director of the stroke center at Duke University, Durham, N.C. He is on the steering committee of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial, which is sponsored by Pfizer. He is also a consultant for Pfizer and Merck. These comments were taken from his editorial accompanying Dr. Westover’s report (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.349]).
Dr. Larry B. Goldstein |
The conclusion of this decision analysis is generally consistent with the data amassed to date: The risks of statin therapy likely outweigh any potential benefit in patients with recent brain hemorrhage, and the drugs should be avoided in this setting, according to Dr. Larry B. Goldstein.
However, any decision analysis is limited by the data on which its assumptions are based. And the clinical trial data concerning risk of recurrent bleeding in this patient population are very sparse.
In particular, the small number of recurrent strokes in different studies of the issue is limiting. Some studies did not distinguish between lobar intracerebral hemorrhage and deep ICH, and as Dr. Westover and his colleagues point out, the risk of ICH recurrence is quite different between these two entities. Some studies were only exploratory, and their results apply only to patients taking very specific statin doses under specific clinical conditions, he noted.
Dr. Goldstein is director of the stroke center at Duke University, Durham, N.C. He is on the steering committee of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial, which is sponsored by Pfizer. He is also a consultant for Pfizer and Merck. These comments were taken from his editorial accompanying Dr. Westover’s report (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.349]).
Clinicians should consider avoiding statins in patients with intracerebral hemorrhage who are at high risk of recurrence because the risks of the drugs appear to outweigh their benefits, according to a report published online Jan. 10 in Archives of Neurology.
After an increased incidence of intracerebral hemorrhage (ICH) was reported among subjects in a randomized clinical trial that evaluated statin therapy, Dr. M. Brandon Westover of the department of neurology at Massachusetts General Hospital and Harvard Medical School, Boston, and his associates developed a mathematical decision analysis model to assess the "common dilemma facing physicians of patients with a history of prior ICH and indications for statin therapy: Under what clinical circumstances should statin therapy be avoided because of risk of recurrent ICH?"
Their analysis indicates that "for lobar ICH in particular, which has a substantially higher recurrence rate than does deep ICH, statin therapy is predicted to increase the baseline annual probability of recurrence from approximately 14% to approximately 22%, offsetting the cardiovascular benefits for both primary and secondary CV prevention."
The model simulated the effects of statin therapy on quality-adjusted life expectancy for a hypothetical 65-year-old male patient under different clinical circumstances. It incorporated published data on risks and benefits.
In the scenario of a patient with a lobar ICH and no prior history of ischemic cerebrovascular or cardiac events, statin therapy yielded 4.6 quality-adjusted life years (QALYs), whereas avoiding statin therapy yielded 6.8 QALYs. Avoiding statins also proved advantageous in all other primary prevention scenarios run by the simulation model.
Similarly, avoiding statins was the preferable course of action in several secondary prevention scenarios featuring a patient with lobar ICH. "These results indicate that the risk of ICH on statin therapy is not offset by the secondary prevention benefits, even if the cardiovascular risks are artificially forced to be extremely high," Dr. Westover and his colleagues wrote.
The model indicated that the risks of statin therapy were substantially lower in hypothetical patients with deep ICH, but still conveyed a net loss of QALYs when used for either primary or secondary prevention.
"Using the base-case assumptions and measuring over a single year of follow-up, primary prevention with statin therapy is projected to prevent fewer than two deaths from either MI or ischemic stroke per 1,000 patients per year, at the expense of causing 18 lobar ICHs (in patients with prior lobar ICH) or 3 deep ICHs (in patients with prior deep ICH) per 1,000 patients per year.
"From the perspective of disability and resulting loss of quality of life, each year of primary prevention with statin treatment saves 2.6 QALYs from myocardial infarction or 2.2 QALYs from ischemic stroke per 1,000 patients per year, at the expense of 58.6 QALYs for lobar ICH or 9 QALYs for deep ICH," they noted (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.356]).
The mechanism by which statins may amplify the risk of hemorrhagic stroke is still unclear, but the drugs are known to have pleiotropic effects independent of their effects on cholesterol levels, which could in turn convey antithrombotic or fibrinolytic changes.
"Mathematical decision analysis of the available data suggests that, because of the high risk of recurrent ICH in survivors of prior hemorrhagic stroke, even a small amplification of this risk by use of statins suffices to recommend that they should be avoided after ICH. In the absence of data from a randomized clinical trial (ideally comparing various agents and doses), the current model provides some guidance for clinicians facing this difficult decision," the investigators said.
The study was supported by the National Institutes of Health. No financial conflicts of interest were reported.
Clinicians should consider avoiding statins in patients with intracerebral hemorrhage who are at high risk of recurrence because the risks of the drugs appear to outweigh their benefits, according to a report published online Jan. 10 in Archives of Neurology.
After an increased incidence of intracerebral hemorrhage (ICH) was reported among subjects in a randomized clinical trial that evaluated statin therapy, Dr. M. Brandon Westover of the department of neurology at Massachusetts General Hospital and Harvard Medical School, Boston, and his associates developed a mathematical decision analysis model to assess the "common dilemma facing physicians of patients with a history of prior ICH and indications for statin therapy: Under what clinical circumstances should statin therapy be avoided because of risk of recurrent ICH?"
Their analysis indicates that "for lobar ICH in particular, which has a substantially higher recurrence rate than does deep ICH, statin therapy is predicted to increase the baseline annual probability of recurrence from approximately 14% to approximately 22%, offsetting the cardiovascular benefits for both primary and secondary CV prevention."
The model simulated the effects of statin therapy on quality-adjusted life expectancy for a hypothetical 65-year-old male patient under different clinical circumstances. It incorporated published data on risks and benefits.
In the scenario of a patient with a lobar ICH and no prior history of ischemic cerebrovascular or cardiac events, statin therapy yielded 4.6 quality-adjusted life years (QALYs), whereas avoiding statin therapy yielded 6.8 QALYs. Avoiding statins also proved advantageous in all other primary prevention scenarios run by the simulation model.
Similarly, avoiding statins was the preferable course of action in several secondary prevention scenarios featuring a patient with lobar ICH. "These results indicate that the risk of ICH on statin therapy is not offset by the secondary prevention benefits, even if the cardiovascular risks are artificially forced to be extremely high," Dr. Westover and his colleagues wrote.
The model indicated that the risks of statin therapy were substantially lower in hypothetical patients with deep ICH, but still conveyed a net loss of QALYs when used for either primary or secondary prevention.
"Using the base-case assumptions and measuring over a single year of follow-up, primary prevention with statin therapy is projected to prevent fewer than two deaths from either MI or ischemic stroke per 1,000 patients per year, at the expense of causing 18 lobar ICHs (in patients with prior lobar ICH) or 3 deep ICHs (in patients with prior deep ICH) per 1,000 patients per year.
"From the perspective of disability and resulting loss of quality of life, each year of primary prevention with statin treatment saves 2.6 QALYs from myocardial infarction or 2.2 QALYs from ischemic stroke per 1,000 patients per year, at the expense of 58.6 QALYs for lobar ICH or 9 QALYs for deep ICH," they noted (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.356]).
The mechanism by which statins may amplify the risk of hemorrhagic stroke is still unclear, but the drugs are known to have pleiotropic effects independent of their effects on cholesterol levels, which could in turn convey antithrombotic or fibrinolytic changes.
"Mathematical decision analysis of the available data suggests that, because of the high risk of recurrent ICH in survivors of prior hemorrhagic stroke, even a small amplification of this risk by use of statins suffices to recommend that they should be avoided after ICH. In the absence of data from a randomized clinical trial (ideally comparing various agents and doses), the current model provides some guidance for clinicians facing this difficult decision," the investigators said.
The study was supported by the National Institutes of Health. No financial conflicts of interest were reported.
FROM ARCHIVES OF NEUROLOGY
Major Finding: Primary prevention of ischemic cerebrovascular or cardiac events with statin therapy for 1 year saved 2.6 QALYs from myocardial infarction or 2.2 QALYs from ischemic stroke per 1,000 patients per year, at the expense of 58.6 QALYs for lobar intracerebral hemorrhage or 9 QALYs for deep intracerebral hemorrhage.
Data Source: Analysis of published data on the risks and benefits of statin therapy after intracerebral hemorrhage using a mathematical decision analysis model.
Disclosures: The study was supported by the National Institutes of Health. No financial conflicts were reported.
Infectious Disease Recommendations Largely Based on Low-Quality Evidence
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
FROM ARCHIVES OF INTERNAL MEDICINE
Major Finding: Only 14% of 4,218 individual recommendations in 41 Infectious Diseases Society of America clinical practice guidelines are based on level I evidence such as that from randomized clinical trials, while more than half are based on level III evidence, such as that from expert opinion or descriptive studies.
Data Source: A review of 41 current IDSA clinical practice guidelines aimed at assessing the quality of evidence on which each recommendation is based.
Disclosures: Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
Infectious Disease Recommendations Largely Based on Low-Quality Evidence
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
"Perhaps the main point we should take from the studies on quality of evidence is to be wary of falling into the trap of ‘cookbook medicine,’?" said Dr. John H. Powers.
"The existence of guidelines is probably better than no guidelines, but guidelines will never replace critical thinking in patient care."
For clinicians, guidelines "may provide a starting point for searching for information, but they are not the finish line.
"As with individual research studies, providers should critically evaluate guidelines and the evidence on which they are based and how relevant recommendations are locally at their institutions and in their patients," he said.
Dr. Powers is with the division of clinical research at the Scientific Applications International Corp. (SAIC) in support of the National Institutes of Health. He reports receiving consulting fees from several pharmaceutical companies. These comments were taken from his editorial accompanying the report by Dr. Lee and Dr. Vielemeyer (Arch. Intern. Med. 2010;171:15-17).
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to a report in the Jan. 10 issue of the Archives of Internal Medicine.
Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, said Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.
"Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data," the investigators noted.
"Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care."
The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.
In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or "dramatic results from uncontrolled experiments" as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that "from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees," the investigators said.
They identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendation and the quality of the evidence supporting it. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).
For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.
The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. "However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only," Dr. Lee and Dr. Vielemeyer said.
In addition, "we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades," they added.
These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also "as benchmarks in the appraisal of quality of care provision," they said.
"We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.
"In such cases, we encourage reviewing the primary literature and using one’s clinical judgment rather than relying solely on recommendations," they concluded.
Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.
FROM ARCHIVES OF INTERNAL MEDICINE
Seniors' Walking Speed May Predict Life Expectancy
Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA
For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person’s age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.
They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.
There were 34,485 study subjects, including "substantial" numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Follow-up ranged from 6 to 21 years, with a median of 14 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.
Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.
A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject’s age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted "exceptional" life expectancy, the investigators said (JAMA 2010;305:50-8).
Gait speed "was especially informative after age 75 years" in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.
The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. "Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power," the researchers said.
However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.
"Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments," they added.
In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.
If gait speed is tracked over time, it can serve as an indicator that new health problems have arisen. It can also be helpful in stratifying risks from surgery or chemotherapy, the investigators said.
The data also suggested that there may be a subpopulation of older adults "who walk very slowly but survive for long periods. It would be valuable to further characterize this subgroup," Dr. Studenski and her associates said.
The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from "Hazzard’s Geriatric Medicine & Gerontology," Sixth Edition, (McGraw Hill, 2009).
The study establishes the validity of gait speed testing, which is inexpensive, objective, easy to interpret, and easy to adopt into clinical practice, said Dr. Matteo Cesari.
In the near future, gait speed may become considered a new "vital sign" that is specifically sensitive in older patients.
The study by Studenski and her colleagues demonstrates that, taken together with patient age and sex, gait speed estimates life expectancy with the same predictive value reported for more complicated models that require much more clinical data, such as concomitant disease, body mass index, blood pressure, and medical history.
The usefulness of assessing gait speed is obvious for geriatricians and primary care physicians, but other specialists may also find it helpful. In particular, oncologists and cardiologists can use gait speed to identify which patients may be eligible for more aggressive interventions because they are chronologically, but not biologically, "old."
Matteo Cesari, M.D., Ph.D., is at Università Campus Bio-Medico, Rome. He reported no financial conflicts of interest. These comments were taken from his editorial accompanying Dr. Studenski’s article (JAMA 2010;305:93-4).
The study establishes the validity of gait speed testing, which is inexpensive, objective, easy to interpret, and easy to adopt into clinical practice, said Dr. Matteo Cesari.
In the near future, gait speed may become considered a new "vital sign" that is specifically sensitive in older patients.
The study by Studenski and her colleagues demonstrates that, taken together with patient age and sex, gait speed estimates life expectancy with the same predictive value reported for more complicated models that require much more clinical data, such as concomitant disease, body mass index, blood pressure, and medical history.
The usefulness of assessing gait speed is obvious for geriatricians and primary care physicians, but other specialists may also find it helpful. In particular, oncologists and cardiologists can use gait speed to identify which patients may be eligible for more aggressive interventions because they are chronologically, but not biologically, "old."
Matteo Cesari, M.D., Ph.D., is at Università Campus Bio-Medico, Rome. He reported no financial conflicts of interest. These comments were taken from his editorial accompanying Dr. Studenski’s article (JAMA 2010;305:93-4).
The study establishes the validity of gait speed testing, which is inexpensive, objective, easy to interpret, and easy to adopt into clinical practice, said Dr. Matteo Cesari.
In the near future, gait speed may become considered a new "vital sign" that is specifically sensitive in older patients.
The study by Studenski and her colleagues demonstrates that, taken together with patient age and sex, gait speed estimates life expectancy with the same predictive value reported for more complicated models that require much more clinical data, such as concomitant disease, body mass index, blood pressure, and medical history.
The usefulness of assessing gait speed is obvious for geriatricians and primary care physicians, but other specialists may also find it helpful. In particular, oncologists and cardiologists can use gait speed to identify which patients may be eligible for more aggressive interventions because they are chronologically, but not biologically, "old."
Matteo Cesari, M.D., Ph.D., is at Università Campus Bio-Medico, Rome. He reported no financial conflicts of interest. These comments were taken from his editorial accompanying Dr. Studenski’s article (JAMA 2010;305:93-4).
Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA
For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person’s age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.
They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.
There were 34,485 study subjects, including "substantial" numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Follow-up ranged from 6 to 21 years, with a median of 14 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.
Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.
A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject’s age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted "exceptional" life expectancy, the investigators said (JAMA 2010;305:50-8).
Gait speed "was especially informative after age 75 years" in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.
The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. "Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power," the researchers said.
However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.
"Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments," they added.
In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.
If gait speed is tracked over time, it can serve as an indicator that new health problems have arisen. It can also be helpful in stratifying risks from surgery or chemotherapy, the investigators said.
The data also suggested that there may be a subpopulation of older adults "who walk very slowly but survive for long periods. It would be valuable to further characterize this subgroup," Dr. Studenski and her associates said.
The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from "Hazzard’s Geriatric Medicine & Gerontology," Sixth Edition, (McGraw Hill, 2009).
Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA
For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person’s age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.
They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.
There were 34,485 study subjects, including "substantial" numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Follow-up ranged from 6 to 21 years, with a median of 14 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.
Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.
A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject’s age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted "exceptional" life expectancy, the investigators said (JAMA 2010;305:50-8).
Gait speed "was especially informative after age 75 years" in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.
The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. "Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power," the researchers said.
However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.
"Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments," they added.
In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.
If gait speed is tracked over time, it can serve as an indicator that new health problems have arisen. It can also be helpful in stratifying risks from surgery or chemotherapy, the investigators said.
The data also suggested that there may be a subpopulation of older adults "who walk very slowly but survive for long periods. It would be valuable to further characterize this subgroup," Dr. Studenski and her associates said.
The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from "Hazzard’s Geriatric Medicine & Gerontology," Sixth Edition, (McGraw Hill, 2009).
FROM JAMA
Major Finding: For patients older than 65 years, a gait speed of 0.8 meters per second correlates with the median life expectancy for their age and sex, while faster gait speeds predict longer life expectancy.
Data Source: A pooled analysis of nine cohort studies that assessed gait speed in older adults and followed them for 6-21 years to track survival.
Disclosures: The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from "Hazzard’s Geriatric Medicine & Gerontology," Sixth Edition (McGraw Hill, 2009).
Nearly a Fourth of Patients Given ICDs Don't Meet Implantation Criteria
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
FROM JAMA
Nearly a Fourth of Patients Given ICDs Don't Meet Implantation Criteria
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
"The cardiovascular care community must act on these data," given their serious implications. "In particular, there was an excess of 4 deaths per 1,000 ICU implants when the device was implanted outside the current guidelines," said Dr. Alan Kadish and Dr. Jeffrey Goldberger.
First, it must be determined "how well the NCDR captures some of the subtleties of ICD indications and whether reasons for deviations from the guidelines can be captured accurately." After all, there must be some background rate of ICD implantation outside of guideline recommendations that is clinically indicated; it is just unclear at this time what that background rate should be.
Secondly, it is likely that all physicians need intensive training to understand the rationale behind the guidelines and to be informed of alternative approaches for patients who do not meet them. Health care organizations also should assess adherence to the guidelines in their facilities, to improve both the quality of care they provide and to cut costs.
"If properly applied, the findings of the study by Al-Khatib et al may improve practice patterns and outcomes, with the unique opportunity to do so while lowering health care costs," the editorialists noted.
Dr. Kadish is at Touro College, New York. Dr. Goldberger is at Northwestern University Feinberg School of Medicine, Chicago. Dr. Kadish reported ties to Lifewatch, Sanofi, St. Jude CRM, Medtronic, Guidant, and Bard. Dr. Goldberger reported ties to Boston Scientific, Medtronic, St. Jude Medical, and Biotronik. These comments were taken from their editorial accompanying Dr. Al-Khatib’s report (JAMA 2010;305;91-2).
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
Almost one-fourth of the patients enrolled in a national registry who received implantable cardioverter defibrillators in recent years did not meet evidence-based criteria for implantation, according to a report in the Jan. 5 issue of JAMA.
The patients who did not meet these criteria were at significantly increased risk for complications, including death, cardiac tamponade, pneumothorax, infection, and hematoma. The study data suggest that one excess complication developed for every 121 non–evidence-based ICD implantations that occurred.
It is important to note that "these complications resulted from procedures that were not clearly indicated in the first place. While a small risk of complications is acceptable when a procedure has been shown to improve outcomes, no risk is acceptable if a procedure has no demonstrated benefit," said Dr. Sana M. Al-Khatib of Duke Clinical Research Institute, Durham, N.C., and her associates.
The investigators performed what they described as the first national study to examine in-hospital outcomes of patients receiving a non–evidence-based ICD because such outcomes have not been known until now. Even physician adherence to the guidelines in routine clinical practice has not been clear.
Four recommendations in the practice guidelines were of particular concern: ICDs are not indicated in the acute phase after MI, after recent coronary revascularization, in patients with New York Heart Association class IV symptoms, or in those with recently diagnosed heart failure. No benefit with ICD implantation has been demonstrated in these groups, while potential harm is clear.
Dr. Al-Khatib and her colleagues analyzed data on 111,707 implantations done at 1,227 medical centers in 2006-2009 for primary prevention among adults with cardiomyopathy, using the National Cardiovascular Data Registry’s ICD registry. The registry tracks ICD implantations in all Medicare beneficiaries as well as in non-Medicare patients treated at 78% of the 1,448 hospitals enrolled.
They found that 25,145 (22.5%) of the procedures were performed in patients who did not meet evidence-based criteria.
A total of 9,257 ICDs (37% of those implanted contrary to recommendations) were implanted within 40 days of an MI, 814 (3%) were implanted within 3 months of coronary artery bypass graft (CABG) surgery, 3,022 (12%) were implanted in patients with NYHA class IV symptoms, and 15,604 (62%) were implanted in patients newly diagnosed as having heart failure. Because some patients had more than one non–evidence-based criteria, the figures exceed 100%.
Complications were significantly more likely to arise in patients who did not conform to evidence-based criteria for the devices (3.2%) than in those who did (2.4%). In particular, the risk of in-hospital death was 0.57% for patients in whom ICDs were not indicated, significantly higher than the 0.18% risk in patients for whom they were indicated. The median length of hospital stay also was significantly longer (3 days vs. 1 day).
There was no clustering of non–evidence-based implantations at a subset of medical centers, although the distribution of such procedures varied greatly. At many centers, these "nonindicated" implantations comprised more than 40% of the total number performed there. This finding suggests that both hospital sites and individual physicians need to improve adherence to implantation guidelines, Dr. Al-Khatib and her associates said (JAMA 2010;305:43-9).
The number of non–evidence-based implantations also varied by physician specialty.
Electrophysiologists were significantly less likely than were other specialists to implant ICDs in patients in whom the devices were not indicated, with a rate of 21%. The rate for nonelectrophysiologist cardiologists was 25%, that for thoracic surgeons was 36%, and that for general surgeons or other physicians was 25%.
"Future research should investigate [the] reasons behind this disparity [among specialties] and propose ways to decrease non–evidence-based ICD implants," the investigators added.
They noted that some of the "nonindicated" ICD implantations may well have been clinically appropriate, since there are some circumstances in which deviations from the guidelines are allowed. "The guidelines clarify that the ultimate judgment regarding care of a particular patient must be made by the physician and the patient in light of all of the circumstances presented by that patient," Dr. Al-Khatib and her colleagues concluded.
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
FROM JAMA
Major Finding: About 23% of ICD implantations in a national registry were performed in patients for whom there is no evidence of benefit, including patients in the acute phase of MI, those who recently underwent CABG, patients with NYHA class IV symptoms, and those with newly diagnosed heart failure.
Data Source: A retrospective cohort study of 111,707 cases listed in the National Cardiovascular Data Registry’s ICD registry in 2006-2009.
Disclosures: This study was funded by the National Heart, Lung, and Blood Institute. Dr. Al-Khatib reported receiving support from Medtronic and Biotronik, and her associates reported ties to numerous drug and device manufacturers.
Almost All Depressed Adolescents Recover, but Nearly Half Have Recurrence
As many as 97% of all adolescents who are diagnosed as having major depressive disorder recover within 4 years, but nearly half of them have a recurrence during that time, according to a report published online in the Archives of General Psychiatry.
As expected, those who respond well to short-term treatment are more likely to recover. Surprisingly, however, full responders to short-term treatment are no less likely to develop a recurrence than are partial or nonresponders, said John Curry, Ph.D., of the child and family study center at Duke University, Durham, N.C., and his associates.
The investigators sought to characterize both recovery from and recurrences of major depression among adolescents. They performed an extended, 5-year follow-up of 196 subjects who had participated in TADS (Treatment for Adolescents With Depression Study), an 18-week trial that compared responses to fluoxetine, cognitive-behavioral therapy, a combination of the two, and placebo.
The researchers described this as "the largest treatment follow-up sample of depressed adolescents to date."
Approximately 97% of the study subjects recovered from their index episode of major depression. A total of 30% recovered at 6 months, 66% at 12 months, 85% at 18 months, 88% at 24 months, 92% at 30 months, 95% at 36 months, and 97% at 42 months.
As Dr. Curry and his colleagues had hypothesized, recovery at 2 years was significantly more likely to occur among adolescents who had fully responded to short-term treatment (96% recovery rate) than among those who had shown only a partial response or no response in the short term (79% recovery rate). Also as expected, recovery at 2 years was associated with less-severe depression, absence of sleep, or appetite disturbance, as well as better functioning during the depressive episode.
Of the 189 patients who recovered, 101 (53%) remained well throughout 5 years of follow-up, whereas 88 (47%) had a recurrence. Most of these patients had only a single recurrence, but 12 patients had two recurrences and 2 patients had three recurrences during that time. The cumulative recurrence rates were approximately 2% at 1 year post diagnosis, 12% at 2 years, 30% at 3 years, and 38% at 4 years, the investigators said (Arch. Gen. Psychiatry 2010 Nov. 1 [doi:10.1001/archgenpsychiatry.2010.150]).
The mean interval between recovery and onset of a first recurrence was 22 months.
Contrary to expectations, the recurrence rate among full responders (54%) was not lower than that among nonresponders or partial responders (46%). Also unexpected was the finding that patients who received the optimal therapy from the start – fluoxetine plus CBT – had a recurrence rate (49%) that was not significantly different from that of patients who had first been treated with less-than-optimal therapy or even placebo (46%).
Female sex proved to be the most robust predictor of recurrence. "To our knowledge, this is the first study documenting higher recurrence rates among treated adolescent females," the investigators noted.
In the literature, there is no sex difference in recurrence among adults; a community-based study did show such a difference but only in patients aged 19-23 years. "This age range overlaps ours, suggesting that female vulnerability to recurrence may be age-related." Hormonal factors, low perceived mastery, or a ruminative response style characteristic of females in this age group might be responsible, Dr. Curry and his associates said.
Another possible contributor to this sex difference may be related to anxiety. Concomitant anxiety disorder is a predictor of recurrence, and such disorders were more common among females (28%) than among males (15%) in this study.
The investigators also looked at the emergence of bipolar disorder among this population and found this to be a relatively rare occurrence. In all, 9 females and 3 males (6% of the study subjects overall) were diagnosed as having bipolar disorder during follow-up, and 9 of these 12 had not responded to short-term treatment. Bipolar disorder tended to emerge at the end of follow-up, when subjects were a mean age of 18 years old.
The investigators said the most significant limitation of their study was that slightly fewer than half of the TADS participants took part. "This likely reflects the difficulty of maintaining a sample of adolescents during a period when many are moving away from home," they wrote.
This study was funded by the National Institute of Mental Health. Dr. Curry disclosed ties to the REACH Institute, an organization dedicated to quickly disseminating the latest scientific findings on the mental health of children to professionals and families. His associates disclosed ties to numerous pharmaceutical companies. ☐
As many as 97% of all adolescents who are diagnosed as having major depressive disorder recover within 4 years, but nearly half of them have a recurrence during that time, according to a report published online in the Archives of General Psychiatry.
As expected, those who respond well to short-term treatment are more likely to recover. Surprisingly, however, full responders to short-term treatment are no less likely to develop a recurrence than are partial or nonresponders, said John Curry, Ph.D., of the child and family study center at Duke University, Durham, N.C., and his associates.
The investigators sought to characterize both recovery from and recurrences of major depression among adolescents. They performed an extended, 5-year follow-up of 196 subjects who had participated in TADS (Treatment for Adolescents With Depression Study), an 18-week trial that compared responses to fluoxetine, cognitive-behavioral therapy, a combination of the two, and placebo.
The researchers described this as "the largest treatment follow-up sample of depressed adolescents to date."
Approximately 97% of the study subjects recovered from their index episode of major depression. A total of 30% recovered at 6 months, 66% at 12 months, 85% at 18 months, 88% at 24 months, 92% at 30 months, 95% at 36 months, and 97% at 42 months.
As Dr. Curry and his colleagues had hypothesized, recovery at 2 years was significantly more likely to occur among adolescents who had fully responded to short-term treatment (96% recovery rate) than among those who had shown only a partial response or no response in the short term (79% recovery rate). Also as expected, recovery at 2 years was associated with less-severe depression, absence of sleep, or appetite disturbance, as well as better functioning during the depressive episode.
Of the 189 patients who recovered, 101 (53%) remained well throughout 5 years of follow-up, whereas 88 (47%) had a recurrence. Most of these patients had only a single recurrence, but 12 patients had two recurrences and 2 patients had three recurrences during that time. The cumulative recurrence rates were approximately 2% at 1 year post diagnosis, 12% at 2 years, 30% at 3 years, and 38% at 4 years, the investigators said (Arch. Gen. Psychiatry 2010 Nov. 1 [doi:10.1001/archgenpsychiatry.2010.150]).
The mean interval between recovery and onset of a first recurrence was 22 months.
Contrary to expectations, the recurrence rate among full responders (54%) was not lower than that among nonresponders or partial responders (46%). Also unexpected was the finding that patients who received the optimal therapy from the start – fluoxetine plus CBT – had a recurrence rate (49%) that was not significantly different from that of patients who had first been treated with less-than-optimal therapy or even placebo (46%).
Female sex proved to be the most robust predictor of recurrence. "To our knowledge, this is the first study documenting higher recurrence rates among treated adolescent females," the investigators noted.
In the literature, there is no sex difference in recurrence among adults; a community-based study did show such a difference but only in patients aged 19-23 years. "This age range overlaps ours, suggesting that female vulnerability to recurrence may be age-related." Hormonal factors, low perceived mastery, or a ruminative response style characteristic of females in this age group might be responsible, Dr. Curry and his associates said.
Another possible contributor to this sex difference may be related to anxiety. Concomitant anxiety disorder is a predictor of recurrence, and such disorders were more common among females (28%) than among males (15%) in this study.
The investigators also looked at the emergence of bipolar disorder among this population and found this to be a relatively rare occurrence. In all, 9 females and 3 males (6% of the study subjects overall) were diagnosed as having bipolar disorder during follow-up, and 9 of these 12 had not responded to short-term treatment. Bipolar disorder tended to emerge at the end of follow-up, when subjects were a mean age of 18 years old.
The investigators said the most significant limitation of their study was that slightly fewer than half of the TADS participants took part. "This likely reflects the difficulty of maintaining a sample of adolescents during a period when many are moving away from home," they wrote.
This study was funded by the National Institute of Mental Health. Dr. Curry disclosed ties to the REACH Institute, an organization dedicated to quickly disseminating the latest scientific findings on the mental health of children to professionals and families. His associates disclosed ties to numerous pharmaceutical companies. ☐
As many as 97% of all adolescents who are diagnosed as having major depressive disorder recover within 4 years, but nearly half of them have a recurrence during that time, according to a report published online in the Archives of General Psychiatry.
As expected, those who respond well to short-term treatment are more likely to recover. Surprisingly, however, full responders to short-term treatment are no less likely to develop a recurrence than are partial or nonresponders, said John Curry, Ph.D., of the child and family study center at Duke University, Durham, N.C., and his associates.
The investigators sought to characterize both recovery from and recurrences of major depression among adolescents. They performed an extended, 5-year follow-up of 196 subjects who had participated in TADS (Treatment for Adolescents With Depression Study), an 18-week trial that compared responses to fluoxetine, cognitive-behavioral therapy, a combination of the two, and placebo.
The researchers described this as "the largest treatment follow-up sample of depressed adolescents to date."
Approximately 97% of the study subjects recovered from their index episode of major depression. A total of 30% recovered at 6 months, 66% at 12 months, 85% at 18 months, 88% at 24 months, 92% at 30 months, 95% at 36 months, and 97% at 42 months.
As Dr. Curry and his colleagues had hypothesized, recovery at 2 years was significantly more likely to occur among adolescents who had fully responded to short-term treatment (96% recovery rate) than among those who had shown only a partial response or no response in the short term (79% recovery rate). Also as expected, recovery at 2 years was associated with less-severe depression, absence of sleep, or appetite disturbance, as well as better functioning during the depressive episode.
Of the 189 patients who recovered, 101 (53%) remained well throughout 5 years of follow-up, whereas 88 (47%) had a recurrence. Most of these patients had only a single recurrence, but 12 patients had two recurrences and 2 patients had three recurrences during that time. The cumulative recurrence rates were approximately 2% at 1 year post diagnosis, 12% at 2 years, 30% at 3 years, and 38% at 4 years, the investigators said (Arch. Gen. Psychiatry 2010 Nov. 1 [doi:10.1001/archgenpsychiatry.2010.150]).
The mean interval between recovery and onset of a first recurrence was 22 months.
Contrary to expectations, the recurrence rate among full responders (54%) was not lower than that among nonresponders or partial responders (46%). Also unexpected was the finding that patients who received the optimal therapy from the start – fluoxetine plus CBT – had a recurrence rate (49%) that was not significantly different from that of patients who had first been treated with less-than-optimal therapy or even placebo (46%).
Female sex proved to be the most robust predictor of recurrence. "To our knowledge, this is the first study documenting higher recurrence rates among treated adolescent females," the investigators noted.
In the literature, there is no sex difference in recurrence among adults; a community-based study did show such a difference but only in patients aged 19-23 years. "This age range overlaps ours, suggesting that female vulnerability to recurrence may be age-related." Hormonal factors, low perceived mastery, or a ruminative response style characteristic of females in this age group might be responsible, Dr. Curry and his associates said.
Another possible contributor to this sex difference may be related to anxiety. Concomitant anxiety disorder is a predictor of recurrence, and such disorders were more common among females (28%) than among males (15%) in this study.
The investigators also looked at the emergence of bipolar disorder among this population and found this to be a relatively rare occurrence. In all, 9 females and 3 males (6% of the study subjects overall) were diagnosed as having bipolar disorder during follow-up, and 9 of these 12 had not responded to short-term treatment. Bipolar disorder tended to emerge at the end of follow-up, when subjects were a mean age of 18 years old.
The investigators said the most significant limitation of their study was that slightly fewer than half of the TADS participants took part. "This likely reflects the difficulty of maintaining a sample of adolescents during a period when many are moving away from home," they wrote.
This study was funded by the National Institute of Mental Health. Dr. Curry disclosed ties to the REACH Institute, an organization dedicated to quickly disseminating the latest scientific findings on the mental health of children to professionals and families. His associates disclosed ties to numerous pharmaceutical companies. ☐
FROM THE ARCHIVES OF GENERAL PSYCHIATRY
Major Finding: Almost all (97%) adolescents recover from an index episode of major depression within 4 years, but almost half of them (47%) have a recurrence.
Data Source: A 5-year extended follow-up study of a subset of 196 adolescents with major depression who had participated in the TADS clinical trial.
Disclosures: This study was funded by the National Institute of Mental Health. Dr. Curry disclosed ties to the REACH Institute, an organization dedicated to quickly disseminating the latest scientific findings on the mental health of children to professionals and families. His associates disclosed ties to numerous pharmaceutical companies.
Increasing BMI Linked to Mortality
Major Finding: Among white, nonsmoking, healthy men and women, all-cause mortality rates showed a linear increase in association with increasing BMI.
Data Source: A pooled analysis of 19 prospective cohort studies involving 1.46 million white adults followed for a mean of 10 years, to provide mortality risk estimates associated with BMI.
Disclosures: The study was supported by the National Institutes of Health. One of Dr. de Gonzalez's associates said he received consulting fees from Iovate Health Sciences USA.
Among white adults, both overweight and obesity are associated with increased all-cause mortality, a study has shown.
Mortality is lowest within a body mass index range of 20.0-24.9, said Amy Berrington de Gonzalez, D.Phil., of the division of cancer epidemiology and genetics at the National Institutes of Health, and her associates.
Underweight adults also appear to have a higher rate of all-cause mortality, although that association is not as strong, they said.
Some earlier studies suggested that being overweight (BMI, 25.0-29.9) either was beneficial or had little effect on all-cause mortality, while others found slightly increased risks. These inconsistencies may have been due to confounding by tobacco use or disease-related changes in weight.
“We examined the relationship between BMI and all-cause mortality in a pooled analysis of 19 prospective studies” with at least 5 years of follow-up in which smoking status and prevalent disease could be accounted for, the investigators said. The analysis was restricted to non-Hispanic white adults (mean age, 58 years at baseline) “because the relationship between BMI and mortality may differ across racial and ethnic groups,” Dr. de Gonzalez and her colleagues noted.
The 19 cohorts included 1.46 million people and 160,087 deaths during a median follow-up of 10 years.
A total of 58% of the study subjects were women.
When the analysis excluded smokers and people with prevalent disease, all-cause mortality was lowest at a BMI of 20.0–24.9 among both men and women and rose in a nearly linear fashion as BMI increased.
For example, in women who were overweight (BMI, 25.0–29.9), the estimated hazard ratio was 1.13; this rose to 1.44 for obesity class I (BMI, 30.0–34.9); 1.88 for obesity class II (BMI, 35.0–39.9); and 2.51 for obesity class III (BMI, 40.0–49.9).
Hazard ratios were similar for men, except that they were even higher for obesity classes II and III.
“In our study, there were more than five times as many deaths among participants in the highest obesity categories (BMI of 35.0–39.9 and 40.0–49.9) than in previous studies because severe obesity has become more common,” the investigators wrote. In the United States, the rates of these levels of BMI were estimated to be 11% among men and 17% among women in 2008, they added.
Statistical adjustments for other potential confounders such as alcohol consumption, physical activity level, education level, and marital status only attenuated these estimates slightly (N. Engl. J Med. 2010;363:2211-9).
Hazard ratios also increased for a BMI below 20.0, but the results varied widely according to length of follow-up and level of physical activity. In underweight people, increased mortality “is probably, at least in part, an artifact of preexisting disease,” Dr. de Gonzalez and her associates said.
Major Finding: Among white, nonsmoking, healthy men and women, all-cause mortality rates showed a linear increase in association with increasing BMI.
Data Source: A pooled analysis of 19 prospective cohort studies involving 1.46 million white adults followed for a mean of 10 years, to provide mortality risk estimates associated with BMI.
Disclosures: The study was supported by the National Institutes of Health. One of Dr. de Gonzalez's associates said he received consulting fees from Iovate Health Sciences USA.
Among white adults, both overweight and obesity are associated with increased all-cause mortality, a study has shown.
Mortality is lowest within a body mass index range of 20.0-24.9, said Amy Berrington de Gonzalez, D.Phil., of the division of cancer epidemiology and genetics at the National Institutes of Health, and her associates.
Underweight adults also appear to have a higher rate of all-cause mortality, although that association is not as strong, they said.
Some earlier studies suggested that being overweight (BMI, 25.0-29.9) either was beneficial or had little effect on all-cause mortality, while others found slightly increased risks. These inconsistencies may have been due to confounding by tobacco use or disease-related changes in weight.
“We examined the relationship between BMI and all-cause mortality in a pooled analysis of 19 prospective studies” with at least 5 years of follow-up in which smoking status and prevalent disease could be accounted for, the investigators said. The analysis was restricted to non-Hispanic white adults (mean age, 58 years at baseline) “because the relationship between BMI and mortality may differ across racial and ethnic groups,” Dr. de Gonzalez and her colleagues noted.
The 19 cohorts included 1.46 million people and 160,087 deaths during a median follow-up of 10 years.
A total of 58% of the study subjects were women.
When the analysis excluded smokers and people with prevalent disease, all-cause mortality was lowest at a BMI of 20.0–24.9 among both men and women and rose in a nearly linear fashion as BMI increased.
For example, in women who were overweight (BMI, 25.0–29.9), the estimated hazard ratio was 1.13; this rose to 1.44 for obesity class I (BMI, 30.0–34.9); 1.88 for obesity class II (BMI, 35.0–39.9); and 2.51 for obesity class III (BMI, 40.0–49.9).
Hazard ratios were similar for men, except that they were even higher for obesity classes II and III.
“In our study, there were more than five times as many deaths among participants in the highest obesity categories (BMI of 35.0–39.9 and 40.0–49.9) than in previous studies because severe obesity has become more common,” the investigators wrote. In the United States, the rates of these levels of BMI were estimated to be 11% among men and 17% among women in 2008, they added.
Statistical adjustments for other potential confounders such as alcohol consumption, physical activity level, education level, and marital status only attenuated these estimates slightly (N. Engl. J Med. 2010;363:2211-9).
Hazard ratios also increased for a BMI below 20.0, but the results varied widely according to length of follow-up and level of physical activity. In underweight people, increased mortality “is probably, at least in part, an artifact of preexisting disease,” Dr. de Gonzalez and her associates said.
Major Finding: Among white, nonsmoking, healthy men and women, all-cause mortality rates showed a linear increase in association with increasing BMI.
Data Source: A pooled analysis of 19 prospective cohort studies involving 1.46 million white adults followed for a mean of 10 years, to provide mortality risk estimates associated with BMI.
Disclosures: The study was supported by the National Institutes of Health. One of Dr. de Gonzalez's associates said he received consulting fees from Iovate Health Sciences USA.
Among white adults, both overweight and obesity are associated with increased all-cause mortality, a study has shown.
Mortality is lowest within a body mass index range of 20.0-24.9, said Amy Berrington de Gonzalez, D.Phil., of the division of cancer epidemiology and genetics at the National Institutes of Health, and her associates.
Underweight adults also appear to have a higher rate of all-cause mortality, although that association is not as strong, they said.
Some earlier studies suggested that being overweight (BMI, 25.0-29.9) either was beneficial or had little effect on all-cause mortality, while others found slightly increased risks. These inconsistencies may have been due to confounding by tobacco use or disease-related changes in weight.
“We examined the relationship between BMI and all-cause mortality in a pooled analysis of 19 prospective studies” with at least 5 years of follow-up in which smoking status and prevalent disease could be accounted for, the investigators said. The analysis was restricted to non-Hispanic white adults (mean age, 58 years at baseline) “because the relationship between BMI and mortality may differ across racial and ethnic groups,” Dr. de Gonzalez and her colleagues noted.
The 19 cohorts included 1.46 million people and 160,087 deaths during a median follow-up of 10 years.
A total of 58% of the study subjects were women.
When the analysis excluded smokers and people with prevalent disease, all-cause mortality was lowest at a BMI of 20.0–24.9 among both men and women and rose in a nearly linear fashion as BMI increased.
For example, in women who were overweight (BMI, 25.0–29.9), the estimated hazard ratio was 1.13; this rose to 1.44 for obesity class I (BMI, 30.0–34.9); 1.88 for obesity class II (BMI, 35.0–39.9); and 2.51 for obesity class III (BMI, 40.0–49.9).
Hazard ratios were similar for men, except that they were even higher for obesity classes II and III.
“In our study, there were more than five times as many deaths among participants in the highest obesity categories (BMI of 35.0–39.9 and 40.0–49.9) than in previous studies because severe obesity has become more common,” the investigators wrote. In the United States, the rates of these levels of BMI were estimated to be 11% among men and 17% among women in 2008, they added.
Statistical adjustments for other potential confounders such as alcohol consumption, physical activity level, education level, and marital status only attenuated these estimates slightly (N. Engl. J Med. 2010;363:2211-9).
Hazard ratios also increased for a BMI below 20.0, but the results varied widely according to length of follow-up and level of physical activity. In underweight people, increased mortality “is probably, at least in part, an artifact of preexisting disease,” Dr. de Gonzalez and her associates said.
From the New England Journal of Medicine
Keep Weight Off: Up Protein, Cut Glycemic Load
Major Finding: Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
Data Source: A multinational randomized controlled study of five dietary interventions to maintain weight loss for 6 months in 773 obese adults.
Disclosures: This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.
A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial.
More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.
Diogenes was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.
The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).
The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients.
A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants “were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight,” Dr. Larsen and his colleagues said, adding that “[d]espite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods.”
Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.
Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
These findings show that “even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet,” they said.
View on the News
More Time Will Tell
The main limitation of this study was the relatively short duration of follow-up.
“A 2-kg difference in body weight, by itself, has limited practical implications.
“But a diet that could effectively prevent weight regain over the long term would have major public health significance. In this regard, the 12-month and longer follow-up data will be informative,” Dr. David S. Ludwig and Cara B. Ebbeling, Ph.D., noted.
DR. LUDWIG and DR. EBBELING are with the Optimal Weight for Life Program at Children's Hospital and in the pediatrics department at Harvard University, Boston. These comments were taken from an editorial accompanying Dr. Larsen's report (N. Engl. J. Med. 2010;363:2159-61).
Major Finding: Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
Data Source: A multinational randomized controlled study of five dietary interventions to maintain weight loss for 6 months in 773 obese adults.
Disclosures: This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.
A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial.
More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.
Diogenes was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.
The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).
The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients.
A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants “were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight,” Dr. Larsen and his colleagues said, adding that “[d]espite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods.”
Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.
Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
These findings show that “even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet,” they said.
View on the News
More Time Will Tell
The main limitation of this study was the relatively short duration of follow-up.
“A 2-kg difference in body weight, by itself, has limited practical implications.
“But a diet that could effectively prevent weight regain over the long term would have major public health significance. In this regard, the 12-month and longer follow-up data will be informative,” Dr. David S. Ludwig and Cara B. Ebbeling, Ph.D., noted.
DR. LUDWIG and DR. EBBELING are with the Optimal Weight for Life Program at Children's Hospital and in the pediatrics department at Harvard University, Boston. These comments were taken from an editorial accompanying Dr. Larsen's report (N. Engl. J. Med. 2010;363:2159-61).
Major Finding: Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
Data Source: A multinational randomized controlled study of five dietary interventions to maintain weight loss for 6 months in 773 obese adults.
Disclosures: This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.
A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial.
More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.
Diogenes was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.
The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).
The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients.
A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants “were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight,” Dr. Larsen and his colleagues said, adding that “[d]espite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods.”
Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.
Only subjects assigned to the group with low protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.
These findings show that “even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet,” they said.
View on the News
More Time Will Tell
The main limitation of this study was the relatively short duration of follow-up.
“A 2-kg difference in body weight, by itself, has limited practical implications.
“But a diet that could effectively prevent weight regain over the long term would have major public health significance. In this regard, the 12-month and longer follow-up data will be informative,” Dr. David S. Ludwig and Cara B. Ebbeling, Ph.D., noted.
DR. LUDWIG and DR. EBBELING are with the Optimal Weight for Life Program at Children's Hospital and in the pediatrics department at Harvard University, Boston. These comments were taken from an editorial accompanying Dr. Larsen's report (N. Engl. J. Med. 2010;363:2159-61).
From the New England Journal of Medicine
Cow's Milk Formula May Boost Later Risk of Type 1 Diabetes
Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow's milk–based formula during infancy.
This indicates that “a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible,” said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.
Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.
The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow's milk–based formula made to smell and taste like the intervention formula.
Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.
Blood samples were obtained periodically to test for five autoantibodies.
The intervention formula was linked with a significant decrease in risk of seropositivity for islet-cell antibodies, the tyrosine phosphatase-related insulinoma-associated 2 molecule, or to at least one of the five autoantibodies assessed, which also included insulin antibodies, and antibodies to glutamic acid decarboxylase, and zinc transporter 8, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).
By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to show significance of this measure, they added.
Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow's milk–based formula during infancy.
This indicates that “a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible,” said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.
Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.
The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow's milk–based formula made to smell and taste like the intervention formula.
Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.
Blood samples were obtained periodically to test for five autoantibodies.
The intervention formula was linked with a significant decrease in risk of seropositivity for islet-cell antibodies, the tyrosine phosphatase-related insulinoma-associated 2 molecule, or to at least one of the five autoantibodies assessed, which also included insulin antibodies, and antibodies to glutamic acid decarboxylase, and zinc transporter 8, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).
By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to show significance of this measure, they added.
Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow's milk–based formula during infancy.
This indicates that “a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible,” said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.
Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.
The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow's milk–based formula made to smell and taste like the intervention formula.
Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.
Blood samples were obtained periodically to test for five autoantibodies.
The intervention formula was linked with a significant decrease in risk of seropositivity for islet-cell antibodies, the tyrosine phosphatase-related insulinoma-associated 2 molecule, or to at least one of the five autoantibodies assessed, which also included insulin antibodies, and antibodies to glutamic acid decarboxylase, and zinc transporter 8, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).
By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to show significance of this measure, they added.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major Finding: Neonates who received casein-based formula were
significantly less likely to develop signs of beta-cell autoimmunity by
age 10 years than were those who received standard cow's milk–based
formula.
Data Source: A multicenter Finnish pilot study in
230 neonates randomly assigned to receive an intervention or a control
formula for at least 6 months, then followed for up to 10 years.
Disclosures:
Funding was by the Academy of Finland, the European Commission, the
Juvenile Diabetes Foundation, the Novo Nordisk Foundation, and several
other nonindustry sources. Infant formulas were provided by Mead Johnson
Nutrition. The researchers had no conflicts of interest.