Mary Ann Moon

Adding hemoglobin A_1c level to traditional cardiovascular risk factors doesn’t improve the prediction of incident cardiovascular disease among middle-age and older adults who don’t have diabetes, according to a large analysis published online March 25 in JAMA.

Some guidelines have suggested that it may be helpful to include information on glycemia measures such as HbA_1c in models that predict CVD risk, even among patients who don’t have diabetes, said Dr. Emanuele Di Angelantonio of the University of Cambridge (U.K.) and his associates in the Emerging Risk Factors Collaboration.

To determine whether or not HbA_1c would improve risk assessment for CVD, they analyzed data collected for 294,998 participants in 73 prospective cohort studies conducted in 20 countries, which recorded incident cardiovascular events during a median follow-up of 10 years. None of the study subjects had diabetes; approximately 86% lived in Europe or North America, and the mean age at baseline was 58 years.

There was a J-shaped association between HbA_1c and CVD risk. However, in several different statistical analyses of the data, HbA_1c levels did not add to CVD risk assessment in a clinically meaningful way. HbA_1c levels did nothing to help distinguish participants who developed CVD from those who did not. And adding HbA_1c values to other, traditional cardiovascular risk factors did not result in reclassification of study participants from one risk category to another, the investigators said (JAMA 2014 March 25 [doi:10.1001/jama.2014.1873]).

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, the U.K. National Institute of Health Research, and the Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Lead-Up Medical Network, Merck, John Wiley & Sons, Elsevier, and Pfizer; his associates reported ties to numerous industry sources.

Adding hemoglobin A_1c level to traditional cardiovascular risk factors doesn’t improve the prediction of incident cardiovascular disease among middle-age and older adults who don’t have diabetes, according to a large analysis published online March 25 in JAMA.

Some guidelines have suggested that it may be helpful to include information on glycemia measures such as HbA_1c in models that predict CVD risk, even among patients who don’t have diabetes, said Dr. Emanuele Di Angelantonio of the University of Cambridge (U.K.) and his associates in the Emerging Risk Factors Collaboration.

To determine whether or not HbA_1c would improve risk assessment for CVD, they analyzed data collected for 294,998 participants in 73 prospective cohort studies conducted in 20 countries, which recorded incident cardiovascular events during a median follow-up of 10 years. None of the study subjects had diabetes; approximately 86% lived in Europe or North America, and the mean age at baseline was 58 years.

There was a J-shaped association between HbA_1c and CVD risk. However, in several different statistical analyses of the data, HbA_1c levels did not add to CVD risk assessment in a clinically meaningful way. HbA_1c levels did nothing to help distinguish participants who developed CVD from those who did not. And adding HbA_1c values to other, traditional cardiovascular risk factors did not result in reclassification of study participants from one risk category to another, the investigators said (JAMA 2014 March 25 [doi:10.1001/jama.2014.1873]).

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, the U.K. National Institute of Health Research, and the Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Lead-Up Medical Network, Merck, John Wiley & Sons, Elsevier, and Pfizer; his associates reported ties to numerous industry sources.

Adding hemoglobin A_1c level to traditional cardiovascular risk factors doesn’t improve the prediction of incident cardiovascular disease among middle-age and older adults who don’t have diabetes, according to a large analysis published online March 25 in JAMA.

Some guidelines have suggested that it may be helpful to include information on glycemia measures such as HbA_1c in models that predict CVD risk, even among patients who don’t have diabetes, said Dr. Emanuele Di Angelantonio of the University of Cambridge (U.K.) and his associates in the Emerging Risk Factors Collaboration.

To determine whether or not HbA_1c would improve risk assessment for CVD, they analyzed data collected for 294,998 participants in 73 prospective cohort studies conducted in 20 countries, which recorded incident cardiovascular events during a median follow-up of 10 years. None of the study subjects had diabetes; approximately 86% lived in Europe or North America, and the mean age at baseline was 58 years.

There was a J-shaped association between HbA_1c and CVD risk. However, in several different statistical analyses of the data, HbA_1c levels did not add to CVD risk assessment in a clinically meaningful way. HbA_1c levels did nothing to help distinguish participants who developed CVD from those who did not. And adding HbA_1c values to other, traditional cardiovascular risk factors did not result in reclassification of study participants from one risk category to another, the investigators said (JAMA 2014 March 25 [doi:10.1001/jama.2014.1873]).

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, the U.K. National Institute of Health Research, and the Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Lead-Up Medical Network, Merck, John Wiley & Sons, Elsevier, and Pfizer; his associates reported ties to numerous industry sources.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

School-aged children who had received high-frequency oscillatory ventilation when they were born extremely prematurely showed modestly better lung function compared with those who had received conventional ventilation at birth, according to researchers.

Neurodevelopmental outcomes were comparable between the two groups.

The report was published online March 19 in the New England Journal of Medicine.

In high-frequency oscillatory ventilation (HFOV), "a constant pressure is applied to improve lung volume and oxygenation, while ventilation is achieved with the use of very low tidal volumes." This strategy was compared against conventional ventilation in a randomized trial of 1-year outcomes at 25 medical centers in the United Kingdom, Singapore, and Australia in the early 2000s; the authors now report long-term outcomes in 319 of the participants who are now 11-14 years of age.

The primary long-term outcome – small-airway function as assessed by forced expiratory flow at 75% of the expired vital capacity (FEF-75) – was "significantly, albeit modestly" better after HFOV than after conventional ventilation. Results also were slightly better for other FEF measures, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, and diffusing capacity, said Dr. Sanja Zivanovic of the Medical Research Council Centre for Allergic Mechanisms in Asthma at King’s College, London, and her associates.

The differences in lung-function measures were small, with an average of approximately 0.3 standard deviations. However, in a further analysis, 47% of the conventional-ventilation group fell below the 10th percentile for FEF-75, compared with only 37% of the HFOV group. This represents "a difference that is likely, in our opinion, to be of clinical importance," the investigators said (N. Engl. J. Med. 2014;370:1121-30 [doi:10.1056/NEJMoa1309220]).

"The poorer lung function in the conventional-ventilation group than in the HFOV group may have consequences over time – for example, by causing greater vulnerability to lung-function insults such a smoking," they noted.

"We were concerned that any respiratory benefit associated with the use of HFOV might have been associated with adverse neurodevelopmental outcomes, because in some trials HFOV has been associated with an increased risk of neonatal brain injury." However, no differences were found between the two study groups in health-related quality of life or behavior, and teachers rated the HFOV group as significantly better at art and design, information technology, and design and technology, "suggesting the possibility that visuospatial skills were better in that group than in the conventional-ventilation group," Dr. Zivanovic and her associates said.

This study was supported by the National Institute for Health Research Health Technology Assessment Programme, the South London Comprehensive Local Research Network, the Department of Health NIHR Biomedical Research Centre, and NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Dr. Zivanovic reported no financial conflicts of interest; some of her associates reported ties to Abbott Laboratories, Bear Medical Systems, SLE Ltd., and Novartis.

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Neuroimaging still is "substantially overused" for outpatients with headache, and its use is increasing despite the publication of numerous guidelines recommending against it in this patient population, according to an analysis of data from the National Ambulatory Medical Care Survey.

Dr. Brian C. Callaghan of the department of neurology at the University of Michigan, Ann Arbor, and his associates sought to use the survey data to characterize recent trends in the use of CT or MRI for routine headache visits to primary care physicians (54.8% of visits), neurologists (19.9%), other specialists (12.9%), and non–primary care generalists (12.4%) in 2007-2010. They identified 51.1 million headache visits, including 25.4 million for migraine.

Neuroimaging was ordered for 12.4% of outpatient headache visits and 9.8% of migraine visits annually, at a cost of nearly $1 billion each year. "Total neuroimaging expenditures were estimated at $3.9 billion over 4 years, including $1.5 billion from migraine visits," they wrote (JAMA Intern. Med. 2014 March 17 [doi:10.1001 /jamainternmed.2014.173]).

© Monkey Business Images Ltd./Thinkstockphotos.com

In a temporal analysis of the data, the researchers found that the rate of neuroimaging rose from 5.1% of all annual headache visits in 1995 to 14.7% in 2010. This increase occurred even though since the year 2000, "multiple guidelines have recommended against routine neuroimaging in patients with headache because a serious intracranial pathologic condition is an uncommon cause." Moreover, the yield of significant abnormalities on neuroimaging of headache patients is only 1%-3%, a rate that is comparable to that in patients without headaches.

"Perhaps guidelines have not curbed utilization because patients, as opposed to health care providers, may be the primary drivers of utilization," Dr. Callaghan and his associates said.

If so, efforts to better inform patients about unwarranted testing or to shift the costs of expensive, low-yield tests to patients may be more effective, they said.

This study was supported by the Katherine Rayner Program, the Taubman Medical Institute, the National Institute of Neurological Disorders and Stroke, and the Agency for Healthcare Research and Quality. Dr. Callaghan and his associates reported no relevant financial conflicts of interest.

Neuroimaging still is "substantially overused" for outpatients with headache, and its use is increasing despite the publication of numerous guidelines recommending against it in this patient population, according to an analysis of data from the National Ambulatory Medical Care Survey.

Dr. Brian C. Callaghan of the department of neurology at the University of Michigan, Ann Arbor, and his associates sought to use the survey data to characterize recent trends in the use of CT or MRI for routine headache visits to primary care physicians (54.8% of visits), neurologists (19.9%), other specialists (12.9%), and non–primary care generalists (12.4%) in 2007-2010. They identified 51.1 million headache visits, including 25.4 million for migraine.

Neuroimaging was ordered for 12.4% of outpatient headache visits and 9.8% of migraine visits annually, at a cost of nearly $1 billion each year. "Total neuroimaging expenditures were estimated at $3.9 billion over 4 years, including $1.5 billion from migraine visits," they wrote (JAMA Intern. Med. 2014 March 17 [doi:10.1001 /jamainternmed.2014.173]).

© Monkey Business Images Ltd./Thinkstockphotos.com

In a temporal analysis of the data, the researchers found that the rate of neuroimaging rose from 5.1% of all annual headache visits in 1995 to 14.7% in 2010. This increase occurred even though since the year 2000, "multiple guidelines have recommended against routine neuroimaging in patients with headache because a serious intracranial pathologic condition is an uncommon cause." Moreover, the yield of significant abnormalities on neuroimaging of headache patients is only 1%-3%, a rate that is comparable to that in patients without headaches.

"Perhaps guidelines have not curbed utilization because patients, as opposed to health care providers, may be the primary drivers of utilization," Dr. Callaghan and his associates said.

If so, efforts to better inform patients about unwarranted testing or to shift the costs of expensive, low-yield tests to patients may be more effective, they said.

This study was supported by the Katherine Rayner Program, the Taubman Medical Institute, the National Institute of Neurological Disorders and Stroke, and the Agency for Healthcare Research and Quality. Dr. Callaghan and his associates reported no relevant financial conflicts of interest.

Neuroimaging still is "substantially overused" for outpatients with headache, and its use is increasing despite the publication of numerous guidelines recommending against it in this patient population, according to an analysis of data from the National Ambulatory Medical Care Survey.

Dr. Brian C. Callaghan of the department of neurology at the University of Michigan, Ann Arbor, and his associates sought to use the survey data to characterize recent trends in the use of CT or MRI for routine headache visits to primary care physicians (54.8% of visits), neurologists (19.9%), other specialists (12.9%), and non–primary care generalists (12.4%) in 2007-2010. They identified 51.1 million headache visits, including 25.4 million for migraine.

Neuroimaging was ordered for 12.4% of outpatient headache visits and 9.8% of migraine visits annually, at a cost of nearly $1 billion each year. "Total neuroimaging expenditures were estimated at $3.9 billion over 4 years, including $1.5 billion from migraine visits," they wrote (JAMA Intern. Med. 2014 March 17 [doi:10.1001 /jamainternmed.2014.173]).

© Monkey Business Images Ltd./Thinkstockphotos.com

In a temporal analysis of the data, the researchers found that the rate of neuroimaging rose from 5.1% of all annual headache visits in 1995 to 14.7% in 2010. This increase occurred even though since the year 2000, "multiple guidelines have recommended against routine neuroimaging in patients with headache because a serious intracranial pathologic condition is an uncommon cause." Moreover, the yield of significant abnormalities on neuroimaging of headache patients is only 1%-3%, a rate that is comparable to that in patients without headaches.

"Perhaps guidelines have not curbed utilization because patients, as opposed to health care providers, may be the primary drivers of utilization," Dr. Callaghan and his associates said.

If so, efforts to better inform patients about unwarranted testing or to shift the costs of expensive, low-yield tests to patients may be more effective, they said.

This study was supported by the Katherine Rayner Program, the Taubman Medical Institute, the National Institute of Neurological Disorders and Stroke, and the Agency for Healthcare Research and Quality. Dr. Callaghan and his associates reported no relevant financial conflicts of interest.

The updated practice guideline for managing adults with valvular heart disease has a new, "modular" format to facilitate clinicians’ access to "concise, relevant bytes of information at the point of care, when clinical knowledge is needed most," according to reports published online simultaneously March 3 in Circulation and the Journal of the American College of Cardiology.

The guideline, compiled by a committee of cardiologists, interventionalists, surgeons, and anesthesiologists under the aegis of the American Heart Association and the American College of Cardiology, was last updated in 2008. "Some recommendations from the earlier valvular heart disease guideline have been updated as warranted by new evidence or a better understanding of earlier evidence, whereas others that were inaccurate, irrelevant, or overlapping were deleted or modified," said writing committee cochairs Dr. Rick A. Nishimura of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn.; and Dr. Catherine M. Otto, director of the University of Washington Medical Center’s Heart Valve Clinic, Seattle.

The narrative text of the guideline is limited, and instead it uses decision pathway diagrams and numerous summary tables of current evidence and recommendations. These include links to relevant references. It is hoped that clinicians can more easily use the new guideline as a quick reference. This format also will enable individual sections to be updated or amended as new evidence comes to light. The PDF of the guideline is available for free.

"This novel approach to evidence-based guideline development will revolutionize the clinical impact of guideline recommendations, ensuring they are always current and allowing seamless integration with electronic medical record systems," Dr. Otto said in a press statement accompanying the reports.

The guideline now includes gradations of disease severity, to help clinicians determine the optimal timing of intervention. Whether or not intervention is indicated depends on five factors: the presence or absence of symptoms, the severity of valvular heart disease, the response of the left and/or right ventricle to the volume or pressure overload caused by the valvular disease, the effect on the pulmonary or systemic circulation, and any change in heart rhythm.

Disease severity ranges from stage A, "at risk," which denotes patients who have risk factors for developing valvular heart disease; through stage B, "progressive," which indicates patients who are asymptomatic but have mildly to moderately severe disease; through stage C, "asymptomatic severe," which includes patients with severe yet still asymptomatic valvular disease in which the left or right ventricle remains compensated or in which the left or right ventricle has decompensated; to stage D, "symptomatic severe," which indicates patients whose severe valvular disease has produced symptoms.

"In patients with stenotic lesions, there is an additional category of ‘very severe’ stenosis based on studies of the natural history showing that prognosis becomes poorer as the severity of stenosis increases," the guideline states.

Information is provided for assessing the various disease states associated with the aortic, mitral, and tricuspid valves, and addresses the issues of valve repair, replacement, and the use of prosthetic valves.

Compared with the previous guideline, the new one suggests surgical intervention at an earlier stage for certain patients. "Due to more knowledge regarding the natural history of untreated patients with severe valvular heart disease and better outcomes from surgery, we’ve lowered the threshold for operation to include more patients with asymptomatic severe disease. Now, select patients with severe asymptomatic aortic stenosis and severe asymptomatic mitral regurgitation can be considered for intervention, depending on certain other factors such as operative mortality and ... the ability to achieve a durable valve repair," Dr. Nishimura said in the press statement.

The new guideline also proposes a new approach to risk assessment, to be applied to all patients for whom intervention is being considered. Previous risk scoring systems were "useful but limited"; the new approach takes into consideration "procedure-specific impediments, major organ system compromise, comorbidities, patient frailty, and the Society of Thoracic Surgeons predicted risk of mortality model."

For the first time, the guideline discusses transcatheter aortic valve replacement and other catheter-based treatments, new technologies that have improved patient care but also have complicated risk assessment. Separate recommendations are now offered regarding the choice and the timing of these interventions.

In addition to the AHA and the ACC, this guideline was developed in collaboration with the American Association for Thoracic Surgery, American Society for Echocardiography, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons.

The complete 2014 Guideline for the Management of Patients With Valvular Heart Disease is available from the American College of Cardiology and the American Heart Association.

Dr. Nishimura and Dr. Otto reported no financial conflicts of interest; their associates on the ACC/AHA Task Force’s writing committee reported ties to Edwards Scientific, Medtronic, and St. Jude Medical.

The updated practice guideline for managing adults with valvular heart disease has a new, "modular" format to facilitate clinicians’ access to "concise, relevant bytes of information at the point of care, when clinical knowledge is needed most," according to reports published online simultaneously March 3 in Circulation and the Journal of the American College of Cardiology.

The guideline, compiled by a committee of cardiologists, interventionalists, surgeons, and anesthesiologists under the aegis of the American Heart Association and the American College of Cardiology, was last updated in 2008. "Some recommendations from the earlier valvular heart disease guideline have been updated as warranted by new evidence or a better understanding of earlier evidence, whereas others that were inaccurate, irrelevant, or overlapping were deleted or modified," said writing committee cochairs Dr. Rick A. Nishimura of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn.; and Dr. Catherine M. Otto, director of the University of Washington Medical Center’s Heart Valve Clinic, Seattle.

The narrative text of the guideline is limited, and instead it uses decision pathway diagrams and numerous summary tables of current evidence and recommendations. These include links to relevant references. It is hoped that clinicians can more easily use the new guideline as a quick reference. This format also will enable individual sections to be updated or amended as new evidence comes to light. The PDF of the guideline is available for free.

"This novel approach to evidence-based guideline development will revolutionize the clinical impact of guideline recommendations, ensuring they are always current and allowing seamless integration with electronic medical record systems," Dr. Otto said in a press statement accompanying the reports.

The guideline now includes gradations of disease severity, to help clinicians determine the optimal timing of intervention. Whether or not intervention is indicated depends on five factors: the presence or absence of symptoms, the severity of valvular heart disease, the response of the left and/or right ventricle to the volume or pressure overload caused by the valvular disease, the effect on the pulmonary or systemic circulation, and any change in heart rhythm.

Disease severity ranges from stage A, "at risk," which denotes patients who have risk factors for developing valvular heart disease; through stage B, "progressive," which indicates patients who are asymptomatic but have mildly to moderately severe disease; through stage C, "asymptomatic severe," which includes patients with severe yet still asymptomatic valvular disease in which the left or right ventricle remains compensated or in which the left or right ventricle has decompensated; to stage D, "symptomatic severe," which indicates patients whose severe valvular disease has produced symptoms.

"In patients with stenotic lesions, there is an additional category of ‘very severe’ stenosis based on studies of the natural history showing that prognosis becomes poorer as the severity of stenosis increases," the guideline states.

Information is provided for assessing the various disease states associated with the aortic, mitral, and tricuspid valves, and addresses the issues of valve repair, replacement, and the use of prosthetic valves.

Compared with the previous guideline, the new one suggests surgical intervention at an earlier stage for certain patients. "Due to more knowledge regarding the natural history of untreated patients with severe valvular heart disease and better outcomes from surgery, we’ve lowered the threshold for operation to include more patients with asymptomatic severe disease. Now, select patients with severe asymptomatic aortic stenosis and severe asymptomatic mitral regurgitation can be considered for intervention, depending on certain other factors such as operative mortality and ... the ability to achieve a durable valve repair," Dr. Nishimura said in the press statement.

The new guideline also proposes a new approach to risk assessment, to be applied to all patients for whom intervention is being considered. Previous risk scoring systems were "useful but limited"; the new approach takes into consideration "procedure-specific impediments, major organ system compromise, comorbidities, patient frailty, and the Society of Thoracic Surgeons predicted risk of mortality model."

For the first time, the guideline discusses transcatheter aortic valve replacement and other catheter-based treatments, new technologies that have improved patient care but also have complicated risk assessment. Separate recommendations are now offered regarding the choice and the timing of these interventions.

In addition to the AHA and the ACC, this guideline was developed in collaboration with the American Association for Thoracic Surgery, American Society for Echocardiography, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons.

The complete 2014 Guideline for the Management of Patients With Valvular Heart Disease is available from the American College of Cardiology and the American Heart Association.

Dr. Nishimura and Dr. Otto reported no financial conflicts of interest; their associates on the ACC/AHA Task Force’s writing committee reported ties to Edwards Scientific, Medtronic, and St. Jude Medical.

The updated practice guideline for managing adults with valvular heart disease has a new, "modular" format to facilitate clinicians’ access to "concise, relevant bytes of information at the point of care, when clinical knowledge is needed most," according to reports published online simultaneously March 3 in Circulation and the Journal of the American College of Cardiology.

The guideline, compiled by a committee of cardiologists, interventionalists, surgeons, and anesthesiologists under the aegis of the American Heart Association and the American College of Cardiology, was last updated in 2008. "Some recommendations from the earlier valvular heart disease guideline have been updated as warranted by new evidence or a better understanding of earlier evidence, whereas others that were inaccurate, irrelevant, or overlapping were deleted or modified," said writing committee cochairs Dr. Rick A. Nishimura of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn.; and Dr. Catherine M. Otto, director of the University of Washington Medical Center’s Heart Valve Clinic, Seattle.

The narrative text of the guideline is limited, and instead it uses decision pathway diagrams and numerous summary tables of current evidence and recommendations. These include links to relevant references. It is hoped that clinicians can more easily use the new guideline as a quick reference. This format also will enable individual sections to be updated or amended as new evidence comes to light. The PDF of the guideline is available for free.

"This novel approach to evidence-based guideline development will revolutionize the clinical impact of guideline recommendations, ensuring they are always current and allowing seamless integration with electronic medical record systems," Dr. Otto said in a press statement accompanying the reports.

The guideline now includes gradations of disease severity, to help clinicians determine the optimal timing of intervention. Whether or not intervention is indicated depends on five factors: the presence or absence of symptoms, the severity of valvular heart disease, the response of the left and/or right ventricle to the volume or pressure overload caused by the valvular disease, the effect on the pulmonary or systemic circulation, and any change in heart rhythm.

Disease severity ranges from stage A, "at risk," which denotes patients who have risk factors for developing valvular heart disease; through stage B, "progressive," which indicates patients who are asymptomatic but have mildly to moderately severe disease; through stage C, "asymptomatic severe," which includes patients with severe yet still asymptomatic valvular disease in which the left or right ventricle remains compensated or in which the left or right ventricle has decompensated; to stage D, "symptomatic severe," which indicates patients whose severe valvular disease has produced symptoms.

"In patients with stenotic lesions, there is an additional category of ‘very severe’ stenosis based on studies of the natural history showing that prognosis becomes poorer as the severity of stenosis increases," the guideline states.

Information is provided for assessing the various disease states associated with the aortic, mitral, and tricuspid valves, and addresses the issues of valve repair, replacement, and the use of prosthetic valves.

Compared with the previous guideline, the new one suggests surgical intervention at an earlier stage for certain patients. "Due to more knowledge regarding the natural history of untreated patients with severe valvular heart disease and better outcomes from surgery, we’ve lowered the threshold for operation to include more patients with asymptomatic severe disease. Now, select patients with severe asymptomatic aortic stenosis and severe asymptomatic mitral regurgitation can be considered for intervention, depending on certain other factors such as operative mortality and ... the ability to achieve a durable valve repair," Dr. Nishimura said in the press statement.

The new guideline also proposes a new approach to risk assessment, to be applied to all patients for whom intervention is being considered. Previous risk scoring systems were "useful but limited"; the new approach takes into consideration "procedure-specific impediments, major organ system compromise, comorbidities, patient frailty, and the Society of Thoracic Surgeons predicted risk of mortality model."

For the first time, the guideline discusses transcatheter aortic valve replacement and other catheter-based treatments, new technologies that have improved patient care but also have complicated risk assessment. Separate recommendations are now offered regarding the choice and the timing of these interventions.

In addition to the AHA and the ACC, this guideline was developed in collaboration with the American Association for Thoracic Surgery, American Society for Echocardiography, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons.

The complete 2014 Guideline for the Management of Patients With Valvular Heart Disease is available from the American College of Cardiology and the American Heart Association.

Dr. Nishimura and Dr. Otto reported no financial conflicts of interest; their associates on the ACC/AHA Task Force’s writing committee reported ties to Edwards Scientific, Medtronic, and St. Jude Medical.

Oral pregabalin significantly improved symptoms of moderate to severe restless leg syndrome, compared with both placebo and pramipexole, in an industry-sponsored, international randomized trial.

Just as important, pregabalin was associated with significantly less iatrogenic worsening, or augmentation, of symptoms than was pramipexole, Richard P. Allen, Ph.D., of the department of neurology at Johns Hopkins University, Baltimore, and his associates reported in the New England Journal of Medicine.

Pregabalin also was associated with lower rates of nausea, vomiting, and headache than pramipexole, but patients taking pregabalin had higher rates of suicidal ideation, dizziness, somnolence, and weight gain – "factors that may limit its long-term use," the investigators said.

Dopaminergic drugs such as pramipexole are known to be associated with augmentation in which symptoms intensify and may involve more parts of the body and start earlier in the day than before treatment. Pregabalin is a nondopaminergic agent with analgesic and anticonvulsant activity, and was recently reported to be effective against restless leg syndrome.

Dr. Allen and his colleagues assessed both agents in a study involving 719 adults with moderate to severe primary restless leg syndrome. The patients did not undergo an objective assessment of sleep.

In the double-blind trial sponsored by Pfizer, the manufacturer of pregabalin, these patients were randomly assigned to receive 0.25 mg pramipexole, 0.5 mg pramipexole, 300 mg pregabalin, or matching placebo capsules every day for 12 weeks. At that time, all patients receiving placebo were randomly reassigned to one of the three active treatments for the remainder (40 weeks) of the 1-year study. The mean age of the patients ranged from 54 to 57 years in the groups.

Periodically, participants reviewed with clinicians their daily symptom logs and completed the International RLS (IRLS) Study Group Rating Scale, which measures subjective symptom severity on a 0-40 scale, with higher scores indicating worse symptoms.

Clinicians also assessed patients’ symptoms using the Clinical Global Impression of Improvement (CGI-I) scale, and they assessed possible augmentation using their clinical judgment, scores on the Augmentation Severity Rating Scale, and scores on the Structured Interview for the Diagnosis of Augmentation instrument.

At 12 weeks, patients who received pregabalin showed significantly greater improvement in IRLS scores than did those who received placebo, improving from 22.3 to 10.9 for pregabalin-treated patients and from 22.4 to 15.5 for placebo-treated patients. Pregabalin-treated patients also were more likely to have "very much improved" or "much improved" ratings on the CGI-I, compared with placebo (71.4% vs 46.8%).

Patients who received pregabalin also reported greater improvement in several sleep parameters, including waking after sleep onset, quality of sleep, and total sleep time, compared with those who received placebo. These measures also were significantly better for patients treated with 0.5 mg pramipexole when compared with placebo-treated patients, but not for those taking 0.25 mg pramipexole.

The finding that pregabalin is effective for RLS even though it has no direct effect on dopaminergic systems calls into question the rationale for dopaminergic therapies. Dopaminergic treatments have been predicated on the assumption that RLS results primarily from dopamine abnormalities, Dr. Allen and his associates noted (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMoa1303646]).

Pregabalin was associated with significantly less augmentation than the 0.5-mg dose of pramipexole, but not the 0.25-mg dose. "Among patients receiving active treatment over the entire 52-week study period, augmentation occurred in 3 of 176 patients receiving pregabalin (1.7%), 11 of 167 receiving 0.25 mg of pramipexole (6.6%), and 16 of 178 receiving 0.5 mg of pramipexole (9.0%)," the investigators wrote.

The rate of discontinuing the study because of adverse events was higher for the patients receiving pregabalin (27.5%) than for those receiving pramipexole at either the lower dose (18.5%) or higher dose (23.9%).

A total of 50 serious adverse events occurred in 37 patients: 16 events in the pregabalin group, 22 events in the lower-dose pramipexole group, and 12 events in the higher-dose pramipexole group. This included 11 cases of suicidal ideation: 6 in the pregabalin group, 3 in the lower-dose pramipexole group, and 2 in the higher-dose pramipexole group.

Dr. Allen reported ties to Pfizer, UCB Pharma, Impax Pharmaceuticals, Luitpold Pharma, Xenoport, GlaxoSmithKline, and Pharmacosmos. His associates reported ties to Pfizer and numerous industry sources. Four authors are employees of Pfizer.

Dr. Sudhansu Chokroverty comments: This carefully conducted study is one of a few head-to-head studies of two classes of medications that have been reported for the treatment of restless leg syndrome. It presents compelling evidence for the efficacy of a nondopaminergic drug in the treatment of RLS and thereby implicates a role for nondopaminergic pathways in the disease, said Dr. Sudhansu Chokroverty.

Although augmentation occurred significantly more often with pramipexole, patients who took pregabalin still had a rate of 1.7%, which "raises the question of whether augmentation is related to medication, is intrinsic to RLS, or is related to individual patient characteristics," he noted.

Dr. Chokroverty is with the department of neurology at the New Jersey Neuroscience Institute, JFK Medical Center, Edison. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Allen’s report (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMe1313155]).

Oral pregabalin significantly improved symptoms of moderate to severe restless leg syndrome, compared with both placebo and pramipexole, in an industry-sponsored, international randomized trial.

Just as important, pregabalin was associated with significantly less iatrogenic worsening, or augmentation, of symptoms than was pramipexole, Richard P. Allen, Ph.D., of the department of neurology at Johns Hopkins University, Baltimore, and his associates reported in the New England Journal of Medicine.

Pregabalin also was associated with lower rates of nausea, vomiting, and headache than pramipexole, but patients taking pregabalin had higher rates of suicidal ideation, dizziness, somnolence, and weight gain – "factors that may limit its long-term use," the investigators said.

Dopaminergic drugs such as pramipexole are known to be associated with augmentation in which symptoms intensify and may involve more parts of the body and start earlier in the day than before treatment. Pregabalin is a nondopaminergic agent with analgesic and anticonvulsant activity, and was recently reported to be effective against restless leg syndrome.

Dr. Allen and his colleagues assessed both agents in a study involving 719 adults with moderate to severe primary restless leg syndrome. The patients did not undergo an objective assessment of sleep.

In the double-blind trial sponsored by Pfizer, the manufacturer of pregabalin, these patients were randomly assigned to receive 0.25 mg pramipexole, 0.5 mg pramipexole, 300 mg pregabalin, or matching placebo capsules every day for 12 weeks. At that time, all patients receiving placebo were randomly reassigned to one of the three active treatments for the remainder (40 weeks) of the 1-year study. The mean age of the patients ranged from 54 to 57 years in the groups.

Periodically, participants reviewed with clinicians their daily symptom logs and completed the International RLS (IRLS) Study Group Rating Scale, which measures subjective symptom severity on a 0-40 scale, with higher scores indicating worse symptoms.

Clinicians also assessed patients’ symptoms using the Clinical Global Impression of Improvement (CGI-I) scale, and they assessed possible augmentation using their clinical judgment, scores on the Augmentation Severity Rating Scale, and scores on the Structured Interview for the Diagnosis of Augmentation instrument.

At 12 weeks, patients who received pregabalin showed significantly greater improvement in IRLS scores than did those who received placebo, improving from 22.3 to 10.9 for pregabalin-treated patients and from 22.4 to 15.5 for placebo-treated patients. Pregabalin-treated patients also were more likely to have "very much improved" or "much improved" ratings on the CGI-I, compared with placebo (71.4% vs 46.8%).

Patients who received pregabalin also reported greater improvement in several sleep parameters, including waking after sleep onset, quality of sleep, and total sleep time, compared with those who received placebo. These measures also were significantly better for patients treated with 0.5 mg pramipexole when compared with placebo-treated patients, but not for those taking 0.25 mg pramipexole.

The finding that pregabalin is effective for RLS even though it has no direct effect on dopaminergic systems calls into question the rationale for dopaminergic therapies. Dopaminergic treatments have been predicated on the assumption that RLS results primarily from dopamine abnormalities, Dr. Allen and his associates noted (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMoa1303646]).

Pregabalin was associated with significantly less augmentation than the 0.5-mg dose of pramipexole, but not the 0.25-mg dose. "Among patients receiving active treatment over the entire 52-week study period, augmentation occurred in 3 of 176 patients receiving pregabalin (1.7%), 11 of 167 receiving 0.25 mg of pramipexole (6.6%), and 16 of 178 receiving 0.5 mg of pramipexole (9.0%)," the investigators wrote.

The rate of discontinuing the study because of adverse events was higher for the patients receiving pregabalin (27.5%) than for those receiving pramipexole at either the lower dose (18.5%) or higher dose (23.9%).

A total of 50 serious adverse events occurred in 37 patients: 16 events in the pregabalin group, 22 events in the lower-dose pramipexole group, and 12 events in the higher-dose pramipexole group. This included 11 cases of suicidal ideation: 6 in the pregabalin group, 3 in the lower-dose pramipexole group, and 2 in the higher-dose pramipexole group.

Dr. Allen reported ties to Pfizer, UCB Pharma, Impax Pharmaceuticals, Luitpold Pharma, Xenoport, GlaxoSmithKline, and Pharmacosmos. His associates reported ties to Pfizer and numerous industry sources. Four authors are employees of Pfizer.

Dr. Sudhansu Chokroverty comments: This carefully conducted study is one of a few head-to-head studies of two classes of medications that have been reported for the treatment of restless leg syndrome. It presents compelling evidence for the efficacy of a nondopaminergic drug in the treatment of RLS and thereby implicates a role for nondopaminergic pathways in the disease, said Dr. Sudhansu Chokroverty.

Although augmentation occurred significantly more often with pramipexole, patients who took pregabalin still had a rate of 1.7%, which "raises the question of whether augmentation is related to medication, is intrinsic to RLS, or is related to individual patient characteristics," he noted.

Dr. Chokroverty is with the department of neurology at the New Jersey Neuroscience Institute, JFK Medical Center, Edison. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Allen’s report (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMe1313155]).

Oral pregabalin significantly improved symptoms of moderate to severe restless leg syndrome, compared with both placebo and pramipexole, in an industry-sponsored, international randomized trial.

Just as important, pregabalin was associated with significantly less iatrogenic worsening, or augmentation, of symptoms than was pramipexole, Richard P. Allen, Ph.D., of the department of neurology at Johns Hopkins University, Baltimore, and his associates reported in the New England Journal of Medicine.

Pregabalin also was associated with lower rates of nausea, vomiting, and headache than pramipexole, but patients taking pregabalin had higher rates of suicidal ideation, dizziness, somnolence, and weight gain – "factors that may limit its long-term use," the investigators said.

Dopaminergic drugs such as pramipexole are known to be associated with augmentation in which symptoms intensify and may involve more parts of the body and start earlier in the day than before treatment. Pregabalin is a nondopaminergic agent with analgesic and anticonvulsant activity, and was recently reported to be effective against restless leg syndrome.

Dr. Allen and his colleagues assessed both agents in a study involving 719 adults with moderate to severe primary restless leg syndrome. The patients did not undergo an objective assessment of sleep.

In the double-blind trial sponsored by Pfizer, the manufacturer of pregabalin, these patients were randomly assigned to receive 0.25 mg pramipexole, 0.5 mg pramipexole, 300 mg pregabalin, or matching placebo capsules every day for 12 weeks. At that time, all patients receiving placebo were randomly reassigned to one of the three active treatments for the remainder (40 weeks) of the 1-year study. The mean age of the patients ranged from 54 to 57 years in the groups.

Periodically, participants reviewed with clinicians their daily symptom logs and completed the International RLS (IRLS) Study Group Rating Scale, which measures subjective symptom severity on a 0-40 scale, with higher scores indicating worse symptoms.

Clinicians also assessed patients’ symptoms using the Clinical Global Impression of Improvement (CGI-I) scale, and they assessed possible augmentation using their clinical judgment, scores on the Augmentation Severity Rating Scale, and scores on the Structured Interview for the Diagnosis of Augmentation instrument.

At 12 weeks, patients who received pregabalin showed significantly greater improvement in IRLS scores than did those who received placebo, improving from 22.3 to 10.9 for pregabalin-treated patients and from 22.4 to 15.5 for placebo-treated patients. Pregabalin-treated patients also were more likely to have "very much improved" or "much improved" ratings on the CGI-I, compared with placebo (71.4% vs 46.8%).

Patients who received pregabalin also reported greater improvement in several sleep parameters, including waking after sleep onset, quality of sleep, and total sleep time, compared with those who received placebo. These measures also were significantly better for patients treated with 0.5 mg pramipexole when compared with placebo-treated patients, but not for those taking 0.25 mg pramipexole.

The finding that pregabalin is effective for RLS even though it has no direct effect on dopaminergic systems calls into question the rationale for dopaminergic therapies. Dopaminergic treatments have been predicated on the assumption that RLS results primarily from dopamine abnormalities, Dr. Allen and his associates noted (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMoa1303646]).

Pregabalin was associated with significantly less augmentation than the 0.5-mg dose of pramipexole, but not the 0.25-mg dose. "Among patients receiving active treatment over the entire 52-week study period, augmentation occurred in 3 of 176 patients receiving pregabalin (1.7%), 11 of 167 receiving 0.25 mg of pramipexole (6.6%), and 16 of 178 receiving 0.5 mg of pramipexole (9.0%)," the investigators wrote.

The rate of discontinuing the study because of adverse events was higher for the patients receiving pregabalin (27.5%) than for those receiving pramipexole at either the lower dose (18.5%) or higher dose (23.9%).

A total of 50 serious adverse events occurred in 37 patients: 16 events in the pregabalin group, 22 events in the lower-dose pramipexole group, and 12 events in the higher-dose pramipexole group. This included 11 cases of suicidal ideation: 6 in the pregabalin group, 3 in the lower-dose pramipexole group, and 2 in the higher-dose pramipexole group.

Dr. Allen reported ties to Pfizer, UCB Pharma, Impax Pharmaceuticals, Luitpold Pharma, Xenoport, GlaxoSmithKline, and Pharmacosmos. His associates reported ties to Pfizer and numerous industry sources. Four authors are employees of Pfizer.

Dr. Sudhansu Chokroverty comments: This carefully conducted study is one of a few head-to-head studies of two classes of medications that have been reported for the treatment of restless leg syndrome. It presents compelling evidence for the efficacy of a nondopaminergic drug in the treatment of RLS and thereby implicates a role for nondopaminergic pathways in the disease, said Dr. Sudhansu Chokroverty.

Although augmentation occurred significantly more often with pramipexole, patients who took pregabalin still had a rate of 1.7%, which "raises the question of whether augmentation is related to medication, is intrinsic to RLS, or is related to individual patient characteristics," he noted.

Dr. Chokroverty is with the department of neurology at the New Jersey Neuroscience Institute, JFK Medical Center, Edison. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Allen’s report (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056/NEJMe1313155]).

The mandatory use of surgical safety checklists at hospitals across Ontario failed to improve operative mortality, surgical complications, readmissions, or emergency department visits within 30 days after hospital discharge, according to a report published March 12 in the New England Journal of Medicine.

In the 3 months following introduction of checklists at 101 hospitals, mortality remained the same across all subgroups studied, including high-risk groups such as elderly patients and those who required emergency procedures, said Dr. David R. Urbach of the Institute for Clinical Evaluative Sciences and the Institute of Health Policy, Management, and Evaluation, University of Toronto, and his associates.

©PixelEmbargo/thinkstockphotos.com

"There may be value in the use of surgical safety checklists, such as enhanced communication and teamwork, and the promotion of a hospital culture in which safety is a high priority; however, these potential benefits did not translate into meaningful improvements in the outcomes we analyzed," they reported.

The investigators studied about 200,000 surgical procedures performed at "virtually all hospitals providing surgical care for the population of Ontario, [allowing] us to obtain an estimate of the effectiveness of surgical safety checklists that is less susceptible to biases from selective reporting."

Of the 92 hospitals that furnished copies of their checklist, 79 used that of the Canadian Patient Safety Institute, 9 used customized lists, and 4 used the World Health Organization checklist.

A total of 97 hospitals reported that they used a special intervention or educational program to implement the checklist, and almost every hospital reported that it achieved nearly 100% compliance. "The lowest reported compliance by a large community hospital during this period was 91.6%," the investigators said.

The primary outcome measure – overall operative mortality – was 0.71% before introduction of the surgical safety checklist and 0.65% afterward, a nonsignificant difference.

The risk of an emergency department visit within 1 month of hospital discharge was 10.44% before the checklist and 10.55% afterward, and the risk of readmission within 1 month of hospital discharge was 3.11% before the checklist and 3.14% afterward. These differences too were nonsignificant.

When the data were analyzed according to individual hospitals, "no hospital had a significant change in operative mortality after checklist introduction. Within-hospital changes in other surgical outcomes were mixed. For example, 6 hospitals had significantly fewer complications after introduction of the checklist, whereas 3 had significantly more complications," the investigators reported (N. Engl. J. Med. 2014;370:1029-38).

When the data were further adjusted to account for other factors that might contribute to surgical outcomes, such as patient income, gender, and urban vs. rural residence, the results did not change appreciably. Subgroup analyses also failed to identify any particular group of surgical patients who benefited from implementation of the checklist.

The study was supported by the Canadian Institutes of Health Research and the Institute for Clinical Evaluative Sciences. Dr. Urbach and his associates reported no financial conflicts of interest.

The mandatory use of surgical safety checklists at hospitals across Ontario failed to improve operative mortality, surgical complications, readmissions, or emergency department visits within 30 days after hospital discharge, according to a report published March 12 in the New England Journal of Medicine.

In the 3 months following introduction of checklists at 101 hospitals, mortality remained the same across all subgroups studied, including high-risk groups such as elderly patients and those who required emergency procedures, said Dr. David R. Urbach of the Institute for Clinical Evaluative Sciences and the Institute of Health Policy, Management, and Evaluation, University of Toronto, and his associates.

©PixelEmbargo/thinkstockphotos.com

"There may be value in the use of surgical safety checklists, such as enhanced communication and teamwork, and the promotion of a hospital culture in which safety is a high priority; however, these potential benefits did not translate into meaningful improvements in the outcomes we analyzed," they reported.

The investigators studied about 200,000 surgical procedures performed at "virtually all hospitals providing surgical care for the population of Ontario, [allowing] us to obtain an estimate of the effectiveness of surgical safety checklists that is less susceptible to biases from selective reporting."

Of the 92 hospitals that furnished copies of their checklist, 79 used that of the Canadian Patient Safety Institute, 9 used customized lists, and 4 used the World Health Organization checklist.

A total of 97 hospitals reported that they used a special intervention or educational program to implement the checklist, and almost every hospital reported that it achieved nearly 100% compliance. "The lowest reported compliance by a large community hospital during this period was 91.6%," the investigators said.

The primary outcome measure – overall operative mortality – was 0.71% before introduction of the surgical safety checklist and 0.65% afterward, a nonsignificant difference.

The risk of an emergency department visit within 1 month of hospital discharge was 10.44% before the checklist and 10.55% afterward, and the risk of readmission within 1 month of hospital discharge was 3.11% before the checklist and 3.14% afterward. These differences too were nonsignificant.

When the data were analyzed according to individual hospitals, "no hospital had a significant change in operative mortality after checklist introduction. Within-hospital changes in other surgical outcomes were mixed. For example, 6 hospitals had significantly fewer complications after introduction of the checklist, whereas 3 had significantly more complications," the investigators reported (N. Engl. J. Med. 2014;370:1029-38).

When the data were further adjusted to account for other factors that might contribute to surgical outcomes, such as patient income, gender, and urban vs. rural residence, the results did not change appreciably. Subgroup analyses also failed to identify any particular group of surgical patients who benefited from implementation of the checklist.

The study was supported by the Canadian Institutes of Health Research and the Institute for Clinical Evaluative Sciences. Dr. Urbach and his associates reported no financial conflicts of interest.

The mandatory use of surgical safety checklists at hospitals across Ontario failed to improve operative mortality, surgical complications, readmissions, or emergency department visits within 30 days after hospital discharge, according to a report published March 12 in the New England Journal of Medicine.

In the 3 months following introduction of checklists at 101 hospitals, mortality remained the same across all subgroups studied, including high-risk groups such as elderly patients and those who required emergency procedures, said Dr. David R. Urbach of the Institute for Clinical Evaluative Sciences and the Institute of Health Policy, Management, and Evaluation, University of Toronto, and his associates.

©PixelEmbargo/thinkstockphotos.com

"There may be value in the use of surgical safety checklists, such as enhanced communication and teamwork, and the promotion of a hospital culture in which safety is a high priority; however, these potential benefits did not translate into meaningful improvements in the outcomes we analyzed," they reported.

The investigators studied about 200,000 surgical procedures performed at "virtually all hospitals providing surgical care for the population of Ontario, [allowing] us to obtain an estimate of the effectiveness of surgical safety checklists that is less susceptible to biases from selective reporting."

Of the 92 hospitals that furnished copies of their checklist, 79 used that of the Canadian Patient Safety Institute, 9 used customized lists, and 4 used the World Health Organization checklist.

A total of 97 hospitals reported that they used a special intervention or educational program to implement the checklist, and almost every hospital reported that it achieved nearly 100% compliance. "The lowest reported compliance by a large community hospital during this period was 91.6%," the investigators said.

The primary outcome measure – overall operative mortality – was 0.71% before introduction of the surgical safety checklist and 0.65% afterward, a nonsignificant difference.

The risk of an emergency department visit within 1 month of hospital discharge was 10.44% before the checklist and 10.55% afterward, and the risk of readmission within 1 month of hospital discharge was 3.11% before the checklist and 3.14% afterward. These differences too were nonsignificant.

When the data were analyzed according to individual hospitals, "no hospital had a significant change in operative mortality after checklist introduction. Within-hospital changes in other surgical outcomes were mixed. For example, 6 hospitals had significantly fewer complications after introduction of the checklist, whereas 3 had significantly more complications," the investigators reported (N. Engl. J. Med. 2014;370:1029-38).

When the data were further adjusted to account for other factors that might contribute to surgical outcomes, such as patient income, gender, and urban vs. rural residence, the results did not change appreciably. Subgroup analyses also failed to identify any particular group of surgical patients who benefited from implementation of the checklist.

The study was supported by the Canadian Institutes of Health Research and the Institute for Clinical Evaluative Sciences. Dr. Urbach and his associates reported no financial conflicts of interest.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

Two-year outcomes were similar between women who underwent transvaginal sacrospinous ligament fixation and those who underwent transvaginal uterosacral ligament suspension to correct apical vaginal or uterine prolapse and stress incontinence in the first randomized trial to compare the two approaches.

The 5-year OPTIMAL (Operations and Pelvic Muscle Training in the Management of Apical Support Loss) trial at nine U.S. medical centers participating in the Pelvic Floor Disorders Network involved 374 women randomly assigned to transvaginal surgery for stage 2 through stage 4 prolapse. A total of 186 underwent sacrospinous ligament fixation (SSLF), while 188 patients underwent uterosacral ligament suspension (ULS).

The women also were separately randomized to receive perioperative behavioral therapy with pelvic floor muscle training or usual perioperative care, wrote Dr. Matthew D. Barber of the department of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic. The report appears in the March 11 issue of JAMA.

At 2-year follow-up, neither surgical approach was superior to the other in the composite primary outcome of the percentage of patients with surgical success: 60.5% for SSLF and 59.2% for ULS. The investigators defined successful surgery as the absence of descent of the vaginal apex more than one-third into the vaginal canal; anterior or posterior vaginal wall descent beyond the hymen; bothersome vaginal bulge symptoms; and further treatment for prolapse. The overall rates of failure were 18% for bothersome vaginal bulge, 17.5% for anterior and/or posterior prolapse, and 5.1% for further treatment such as more surgery or use of a pessary.

The two groups were no different in any secondary outcomes such as blood loss, duration of surgery, length of hospitalization, or postoperative treatment. Serious adverse events including bladder perforation and the formation of vaginal granulation tissue occurred in 16.7% of the SSLF group and 16.5% of the ULS group. There were no significant differences between women who received the behavioral intervention and those who did not, the investigators said (JAMA 2014;311:1023-34).

They noted that 4.3% of the women who underwent SSLF developed persistent pain, confirming previous reports that the procedure may cause acute neurologic pain, particularly buttock pain that may result from gluteal nerve entrapment. This highlights "the need to provide preoperative counseling to patients about this potential risk," Dr. Barber and his associates wrote.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Some of Dr. Barber’s coauthors reported ties to Astellas, Pfizer, GlaxoSmithKline, Uromedica, IDEO, Xanodyne, Renew Medical, American Medical Systems, Ethicon/Johnson & Johnson, Boston Scientific, and Ferring Pharmaceuticals.

Two-year outcomes were similar between women who underwent transvaginal sacrospinous ligament fixation and those who underwent transvaginal uterosacral ligament suspension to correct apical vaginal or uterine prolapse and stress incontinence in the first randomized trial to compare the two approaches.

The 5-year OPTIMAL (Operations and Pelvic Muscle Training in the Management of Apical Support Loss) trial at nine U.S. medical centers participating in the Pelvic Floor Disorders Network involved 374 women randomly assigned to transvaginal surgery for stage 2 through stage 4 prolapse. A total of 186 underwent sacrospinous ligament fixation (SSLF), while 188 patients underwent uterosacral ligament suspension (ULS).

The women also were separately randomized to receive perioperative behavioral therapy with pelvic floor muscle training or usual perioperative care, wrote Dr. Matthew D. Barber of the department of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic. The report appears in the March 11 issue of JAMA.

At 2-year follow-up, neither surgical approach was superior to the other in the composite primary outcome of the percentage of patients with surgical success: 60.5% for SSLF and 59.2% for ULS. The investigators defined successful surgery as the absence of descent of the vaginal apex more than one-third into the vaginal canal; anterior or posterior vaginal wall descent beyond the hymen; bothersome vaginal bulge symptoms; and further treatment for prolapse. The overall rates of failure were 18% for bothersome vaginal bulge, 17.5% for anterior and/or posterior prolapse, and 5.1% for further treatment such as more surgery or use of a pessary.

The two groups were no different in any secondary outcomes such as blood loss, duration of surgery, length of hospitalization, or postoperative treatment. Serious adverse events including bladder perforation and the formation of vaginal granulation tissue occurred in 16.7% of the SSLF group and 16.5% of the ULS group. There were no significant differences between women who received the behavioral intervention and those who did not, the investigators said (JAMA 2014;311:1023-34).

They noted that 4.3% of the women who underwent SSLF developed persistent pain, confirming previous reports that the procedure may cause acute neurologic pain, particularly buttock pain that may result from gluteal nerve entrapment. This highlights "the need to provide preoperative counseling to patients about this potential risk," Dr. Barber and his associates wrote.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Some of Dr. Barber’s coauthors reported ties to Astellas, Pfizer, GlaxoSmithKline, Uromedica, IDEO, Xanodyne, Renew Medical, American Medical Systems, Ethicon/Johnson & Johnson, Boston Scientific, and Ferring Pharmaceuticals.

Two-year outcomes were similar between women who underwent transvaginal sacrospinous ligament fixation and those who underwent transvaginal uterosacral ligament suspension to correct apical vaginal or uterine prolapse and stress incontinence in the first randomized trial to compare the two approaches.

The 5-year OPTIMAL (Operations and Pelvic Muscle Training in the Management of Apical Support Loss) trial at nine U.S. medical centers participating in the Pelvic Floor Disorders Network involved 374 women randomly assigned to transvaginal surgery for stage 2 through stage 4 prolapse. A total of 186 underwent sacrospinous ligament fixation (SSLF), while 188 patients underwent uterosacral ligament suspension (ULS).

The women also were separately randomized to receive perioperative behavioral therapy with pelvic floor muscle training or usual perioperative care, wrote Dr. Matthew D. Barber of the department of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic. The report appears in the March 11 issue of JAMA.

At 2-year follow-up, neither surgical approach was superior to the other in the composite primary outcome of the percentage of patients with surgical success: 60.5% for SSLF and 59.2% for ULS. The investigators defined successful surgery as the absence of descent of the vaginal apex more than one-third into the vaginal canal; anterior or posterior vaginal wall descent beyond the hymen; bothersome vaginal bulge symptoms; and further treatment for prolapse. The overall rates of failure were 18% for bothersome vaginal bulge, 17.5% for anterior and/or posterior prolapse, and 5.1% for further treatment such as more surgery or use of a pessary.

The two groups were no different in any secondary outcomes such as blood loss, duration of surgery, length of hospitalization, or postoperative treatment. Serious adverse events including bladder perforation and the formation of vaginal granulation tissue occurred in 16.7% of the SSLF group and 16.5% of the ULS group. There were no significant differences between women who received the behavioral intervention and those who did not, the investigators said (JAMA 2014;311:1023-34).

They noted that 4.3% of the women who underwent SSLF developed persistent pain, confirming previous reports that the procedure may cause acute neurologic pain, particularly buttock pain that may result from gluteal nerve entrapment. This highlights "the need to provide preoperative counseling to patients about this potential risk," Dr. Barber and his associates wrote.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Some of Dr. Barber’s coauthors reported ties to Astellas, Pfizer, GlaxoSmithKline, Uromedica, IDEO, Xanodyne, Renew Medical, American Medical Systems, Ethicon/Johnson & Johnson, Boston Scientific, and Ferring Pharmaceuticals.