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Yoga improves asthmatics’ quality of life, data review suggests
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
FROM THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS
More connective tissue disease–associated PAH seen in older patients
Patient age contributes to significant differences in the characteristics and etiology of pulmonary arterial hypertension seen in randomized, controlled trials, including more frequent connective tissue disease–associated disease in older patients, according to a post-hoc analysis of trials.
Additionally, older age was associated with worse baseline functional status, worse outcomes in the 6-minute walk distance, and an overall reduced response to treatment, while hemodynamic severity was higher in younger patients.
“Although registry data have shown that idiopathic PAH [pulmonary arterial hypertension] is increasingly recognized in older populations, our analysis shows that idiopathic etiology was less frequent in the older group. In contrast, CTD [connective tissue disease]–associated PAH accounted for a higher proportion of PAH etiology in the oldest age group,” wrote Jonathan A. Rose of Case Western Reserve University, Cleveland, and his colleagues (Chest. 2016;149[5]:1234-44. doi: 10.1016/j.chest.2015.11.008).
The researchers analyzed seven multicenter, randomized, double-blind, placebo-controlled treatment trials for PAH conducted by United Therapeutics and one open-label extension study that involved following patients being treated with subcutaneous treprostinil for 4 additional years. Data from the open-label extension trial and one of the trials were combined and reported as one trial. All trials excluded patients with a history of left-sided heart disease, pulmonary artery wedge pressure (PAWP) greater than 15 mmHg, or pulmonary vascular resistance (PVR) less than 3 Woods units. The researchers categorized the 2,627 patients included in the trials in the following three age groups: 50 years or younger, 51-64 years, and 65 years or older.
Between 53% and 74% of patients in all trials across all age groups had idiopathic PAH, but older patients comprised a significantly smaller proportion of the patients with idiopathic PAH in three of the trials (P = .004) and a significantly higher percentage of the patients with CTD-associated PAH in all of the trials (P less than .001). Across the trials, CTD-associated PAH occurred in 15%-21% of patients 50 years or younger, 25%-40% of those aged 51-64 years, and 27%-49% of those aged 65 years or older.
From baseline to the end in three of the studies, a smaller change in the 6-minute walk distance was seen in older patients and a higher proportion of older patients had an overall decrease in total 6-minute walk distance. Older age remained associated with this outcome measure when only data from treatment-naive patients or the subgroup of patients with CTD-associated PAH were included.
The association between age and lower baseline functional status was observed in four of the trials; A lower proportion of patients in the oldest age group were classified as being of the World Health Organization functional classes I and II, with 9%-32% of patients aged 65 years or older, 10%-33% in those aged 51-64 years, and 16%-43% of those aged 50 years or younger.
Hemodynamic severity was among the areas in which older patients performed better than younger patients, with the oldest age group having lower baseline mean pulmonary artery pressure (mPAP) and PVR in the two trials that measured hemodynamics.
“The difference in the clinical function and hemodynamics in older patients may reflect different mechanisms of disease. Older patients may have diminished cardiopulmonary reserve, and similar degrees of hemodynamic severity manifest with a larger functional impairment. Alternatively, additional comorbidities in older patients may contribute to a larger extent, and clinical function may not be as directly related to hemodynamic severity,” according to the researchers.
Mortality was generally small in these studies and not significantly different among age groups, except for in the open-label extension study of Subcutaneous Infusion of Treprostinil in Patients with PAH (SC-TRE) and the Study of Intravenous Remodulin in Patients in India with PAH (TRUST) trials, which were combined and reported on as one trial (P = .0004).
Nausea was the only adverse effect found to be associated with age in more than one trial, and the relationship between it and age in two trials were inconsistent. While a higher incidence of nausea was found in the oldest age group in the Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (FREEDOM-M) trial (P = .03), a lower incidence of nausea was found in the oldest age group in the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) trial (P = .02).
The analysis was supported by a grant from the National Institutes of Health. Two of the authors, Jody M. Cleveland and Youlan Rao, Ph.D., reported being employees of United Therapeutics, while Dr. Omar A. Minai, another author of the report, serves on the scientific advisory board of United Therapeutics. The other authors declared no conflicts.
Patient age contributes to significant differences in the characteristics and etiology of pulmonary arterial hypertension seen in randomized, controlled trials, including more frequent connective tissue disease–associated disease in older patients, according to a post-hoc analysis of trials.
Additionally, older age was associated with worse baseline functional status, worse outcomes in the 6-minute walk distance, and an overall reduced response to treatment, while hemodynamic severity was higher in younger patients.
“Although registry data have shown that idiopathic PAH [pulmonary arterial hypertension] is increasingly recognized in older populations, our analysis shows that idiopathic etiology was less frequent in the older group. In contrast, CTD [connective tissue disease]–associated PAH accounted for a higher proportion of PAH etiology in the oldest age group,” wrote Jonathan A. Rose of Case Western Reserve University, Cleveland, and his colleagues (Chest. 2016;149[5]:1234-44. doi: 10.1016/j.chest.2015.11.008).
The researchers analyzed seven multicenter, randomized, double-blind, placebo-controlled treatment trials for PAH conducted by United Therapeutics and one open-label extension study that involved following patients being treated with subcutaneous treprostinil for 4 additional years. Data from the open-label extension trial and one of the trials were combined and reported as one trial. All trials excluded patients with a history of left-sided heart disease, pulmonary artery wedge pressure (PAWP) greater than 15 mmHg, or pulmonary vascular resistance (PVR) less than 3 Woods units. The researchers categorized the 2,627 patients included in the trials in the following three age groups: 50 years or younger, 51-64 years, and 65 years or older.
Between 53% and 74% of patients in all trials across all age groups had idiopathic PAH, but older patients comprised a significantly smaller proportion of the patients with idiopathic PAH in three of the trials (P = .004) and a significantly higher percentage of the patients with CTD-associated PAH in all of the trials (P less than .001). Across the trials, CTD-associated PAH occurred in 15%-21% of patients 50 years or younger, 25%-40% of those aged 51-64 years, and 27%-49% of those aged 65 years or older.
From baseline to the end in three of the studies, a smaller change in the 6-minute walk distance was seen in older patients and a higher proportion of older patients had an overall decrease in total 6-minute walk distance. Older age remained associated with this outcome measure when only data from treatment-naive patients or the subgroup of patients with CTD-associated PAH were included.
The association between age and lower baseline functional status was observed in four of the trials; A lower proportion of patients in the oldest age group were classified as being of the World Health Organization functional classes I and II, with 9%-32% of patients aged 65 years or older, 10%-33% in those aged 51-64 years, and 16%-43% of those aged 50 years or younger.
Hemodynamic severity was among the areas in which older patients performed better than younger patients, with the oldest age group having lower baseline mean pulmonary artery pressure (mPAP) and PVR in the two trials that measured hemodynamics.
“The difference in the clinical function and hemodynamics in older patients may reflect different mechanisms of disease. Older patients may have diminished cardiopulmonary reserve, and similar degrees of hemodynamic severity manifest with a larger functional impairment. Alternatively, additional comorbidities in older patients may contribute to a larger extent, and clinical function may not be as directly related to hemodynamic severity,” according to the researchers.
Mortality was generally small in these studies and not significantly different among age groups, except for in the open-label extension study of Subcutaneous Infusion of Treprostinil in Patients with PAH (SC-TRE) and the Study of Intravenous Remodulin in Patients in India with PAH (TRUST) trials, which were combined and reported on as one trial (P = .0004).
Nausea was the only adverse effect found to be associated with age in more than one trial, and the relationship between it and age in two trials were inconsistent. While a higher incidence of nausea was found in the oldest age group in the Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (FREEDOM-M) trial (P = .03), a lower incidence of nausea was found in the oldest age group in the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) trial (P = .02).
The analysis was supported by a grant from the National Institutes of Health. Two of the authors, Jody M. Cleveland and Youlan Rao, Ph.D., reported being employees of United Therapeutics, while Dr. Omar A. Minai, another author of the report, serves on the scientific advisory board of United Therapeutics. The other authors declared no conflicts.
Patient age contributes to significant differences in the characteristics and etiology of pulmonary arterial hypertension seen in randomized, controlled trials, including more frequent connective tissue disease–associated disease in older patients, according to a post-hoc analysis of trials.
Additionally, older age was associated with worse baseline functional status, worse outcomes in the 6-minute walk distance, and an overall reduced response to treatment, while hemodynamic severity was higher in younger patients.
“Although registry data have shown that idiopathic PAH [pulmonary arterial hypertension] is increasingly recognized in older populations, our analysis shows that idiopathic etiology was less frequent in the older group. In contrast, CTD [connective tissue disease]–associated PAH accounted for a higher proportion of PAH etiology in the oldest age group,” wrote Jonathan A. Rose of Case Western Reserve University, Cleveland, and his colleagues (Chest. 2016;149[5]:1234-44. doi: 10.1016/j.chest.2015.11.008).
The researchers analyzed seven multicenter, randomized, double-blind, placebo-controlled treatment trials for PAH conducted by United Therapeutics and one open-label extension study that involved following patients being treated with subcutaneous treprostinil for 4 additional years. Data from the open-label extension trial and one of the trials were combined and reported as one trial. All trials excluded patients with a history of left-sided heart disease, pulmonary artery wedge pressure (PAWP) greater than 15 mmHg, or pulmonary vascular resistance (PVR) less than 3 Woods units. The researchers categorized the 2,627 patients included in the trials in the following three age groups: 50 years or younger, 51-64 years, and 65 years or older.
Between 53% and 74% of patients in all trials across all age groups had idiopathic PAH, but older patients comprised a significantly smaller proportion of the patients with idiopathic PAH in three of the trials (P = .004) and a significantly higher percentage of the patients with CTD-associated PAH in all of the trials (P less than .001). Across the trials, CTD-associated PAH occurred in 15%-21% of patients 50 years or younger, 25%-40% of those aged 51-64 years, and 27%-49% of those aged 65 years or older.
From baseline to the end in three of the studies, a smaller change in the 6-minute walk distance was seen in older patients and a higher proportion of older patients had an overall decrease in total 6-minute walk distance. Older age remained associated with this outcome measure when only data from treatment-naive patients or the subgroup of patients with CTD-associated PAH were included.
The association between age and lower baseline functional status was observed in four of the trials; A lower proportion of patients in the oldest age group were classified as being of the World Health Organization functional classes I and II, with 9%-32% of patients aged 65 years or older, 10%-33% in those aged 51-64 years, and 16%-43% of those aged 50 years or younger.
Hemodynamic severity was among the areas in which older patients performed better than younger patients, with the oldest age group having lower baseline mean pulmonary artery pressure (mPAP) and PVR in the two trials that measured hemodynamics.
“The difference in the clinical function and hemodynamics in older patients may reflect different mechanisms of disease. Older patients may have diminished cardiopulmonary reserve, and similar degrees of hemodynamic severity manifest with a larger functional impairment. Alternatively, additional comorbidities in older patients may contribute to a larger extent, and clinical function may not be as directly related to hemodynamic severity,” according to the researchers.
Mortality was generally small in these studies and not significantly different among age groups, except for in the open-label extension study of Subcutaneous Infusion of Treprostinil in Patients with PAH (SC-TRE) and the Study of Intravenous Remodulin in Patients in India with PAH (TRUST) trials, which were combined and reported on as one trial (P = .0004).
Nausea was the only adverse effect found to be associated with age in more than one trial, and the relationship between it and age in two trials were inconsistent. While a higher incidence of nausea was found in the oldest age group in the Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (FREEDOM-M) trial (P = .03), a lower incidence of nausea was found in the oldest age group in the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) trial (P = .02).
The analysis was supported by a grant from the National Institutes of Health. Two of the authors, Jody M. Cleveland and Youlan Rao, Ph.D., reported being employees of United Therapeutics, while Dr. Omar A. Minai, another author of the report, serves on the scientific advisory board of United Therapeutics. The other authors declared no conflicts.
FROM CHEST
FDA okays glycopyrrolate/formoterol combo for COPD
The Food and Drug Administration has approved glycopyrrolate and formoterol fumarate inhalation aerosol for long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), according to a statement from AstraZeneca.
AstraZeneca is marketing the bronchodilator as Bevespi Aerosphere. The product is a fixed-dose dual bronchodilator delivered through a pressurized, metered-dose inhaler to be used twice daily. Glycopyrrolate, a long-acting muscarinic antagonist, is available as monotherapy. The FDA also has granted the long-acting beta-2 agonist formoterol fumarate tentative approval for use as monotherapy.
The approval of glycopyrrolate/formoterol fumarate 9 mcg/4.8 mcg is based on the PINNACLE trials, which demonstrated the product achieved improvement in morning predose forced expiratory volume in 1 second at 24 weeks (P less than .001), compared with its monotherapy components and placebo, according to AstraZeneca’s statement.
The most common adverse reactions were urinary tract infection and cough. The drug is not indicated for the treatment of asthma or for the relief of acute bronchospasm.
The Food and Drug Administration has approved glycopyrrolate and formoterol fumarate inhalation aerosol for long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), according to a statement from AstraZeneca.
AstraZeneca is marketing the bronchodilator as Bevespi Aerosphere. The product is a fixed-dose dual bronchodilator delivered through a pressurized, metered-dose inhaler to be used twice daily. Glycopyrrolate, a long-acting muscarinic antagonist, is available as monotherapy. The FDA also has granted the long-acting beta-2 agonist formoterol fumarate tentative approval for use as monotherapy.
The approval of glycopyrrolate/formoterol fumarate 9 mcg/4.8 mcg is based on the PINNACLE trials, which demonstrated the product achieved improvement in morning predose forced expiratory volume in 1 second at 24 weeks (P less than .001), compared with its monotherapy components and placebo, according to AstraZeneca’s statement.
The most common adverse reactions were urinary tract infection and cough. The drug is not indicated for the treatment of asthma or for the relief of acute bronchospasm.
The Food and Drug Administration has approved glycopyrrolate and formoterol fumarate inhalation aerosol for long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), according to a statement from AstraZeneca.
AstraZeneca is marketing the bronchodilator as Bevespi Aerosphere. The product is a fixed-dose dual bronchodilator delivered through a pressurized, metered-dose inhaler to be used twice daily. Glycopyrrolate, a long-acting muscarinic antagonist, is available as monotherapy. The FDA also has granted the long-acting beta-2 agonist formoterol fumarate tentative approval for use as monotherapy.
The approval of glycopyrrolate/formoterol fumarate 9 mcg/4.8 mcg is based on the PINNACLE trials, which demonstrated the product achieved improvement in morning predose forced expiratory volume in 1 second at 24 weeks (P less than .001), compared with its monotherapy components and placebo, according to AstraZeneca’s statement.
The most common adverse reactions were urinary tract infection and cough. The drug is not indicated for the treatment of asthma or for the relief of acute bronchospasm.
Reintubation avoided by majority of patients on noninvasive ventilation therapy, high-flow oxygen
Extubated patients who either received noninvasive ventilation (NIV) therapy or high-flow nasal cannula oxygen had a lower risk of reintubation, compared with extubated patients who received some form of standard oxygen therapy, according to the results of two multicenter, randomized clinical trials published online in JAMA.
Participants in one of the studies, which included abdominal surgery patients diagnosed with respiratory failure within 7 days following surgery, either received NIV or standard oxygen therapy for 30 days or until ICU discharge, whichever came first. While NIV has been effectively used to treat nonsurgical patients with acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema, there is no evidence to support the use of NIV in surgical patients with hypoxemic acute respiratory failure after abdominal surgery, according to Dr. Samir Jaber of the Saint Eloi University Hospital and Montpellier School of Medicine, both in Montpellier, France, and his colleagues (JAMA. 2016 Apr 5;315[13]:1345-53).
The second study included adult patients who had received mechanical ventilation for more than 12 hours and who met criteria for being considered at low risk for reintubation. Patients were administered either high-flow oxygen therapy through nasal cannula immediately after extubation or continuous conventional oxygen therapy through nasal cannula or nonrebreather facemask; the patients were observed for 72 hours. High-flow therapy has been shown to improve oxygenation and survival in clinical studies of critically ill patients in the acute phase of respiratory failure. “[A study by S.M. Maggiore and his colleagues (Am J Respir Crit Care Med. 2014;190(3):282-8)] suggested that high-flow therapy after planned extubation decreased the reintubation rate in a general population of critical patients, but the benefits might be mainly attributable to improvements in high-risk patients,” said Dr. Gonzalo Hernandez, of the Hospital Virgen de la Salud, Toledo, Spain, and his colleagues (JAMA. 2016 Apr 5;315[13]:1354-61).
In the first study, 148 patients received NIV and 145 patients received standard oxygen therapy only. NIV was administered through a facemask connected to an ICU- or a NIV-dedicated ventilator, using either a heated humidifier or heat and moisture exchanger to warm and humidify inspired gases. Patients were encouraged to use NIV for 6 hours during the first 24 hours of the study and received standard oxygen therapy at a rate of up to 15 L/minute to maintain an arterial oxygen saturation estimate (SpO2) of at least 94% in between NIV sessions. NIV was started at an inspiratory positive airway pressure of 5 cm H2O, increasing to a maximum inspiratory pressure of 15 cm H2O, aiming to achieve an expiratory tidal volume between 6 and 8 mL/kg of predicted body weight and a respiratory rate lower than 25/min. The patients in this study’s control group only received the standard oxygen therapy.
In the other study, 263 patients received conventional therapy, with the oxygen flow having been adjusted to maintain an arterial oxygen saturation estimate of greater than 92%. This study’s other 264 patients received high-flow oxygen therapy, with the flow having been initially set at 10 L/min and titrated upward in 5-L/min steps until patients experienced discomfort. The high-flow therapy was stopped after 24 hours and was followed by conventional oxygen therapy, when needed.
The primary outcome measure in the study involving NIV was cause for reintubation within 7 days of randomization.
Secondary outcome measures included gas exchange, healthcare-associated infection rate within 30 days, number of ventilator-free days between days 1 and 30, antibiotic use duration, ICU and in-hospital length of stay, and 30- and 90-day mortality.
Reintubation occurred in 49 patients in the NIV group and 66 patients in the standard oxygen therapy group, a significant difference (P = .03). Among the reintubated patients, those who had received NIV spent less time under invasive mechanical ventilation as did the patients given standard oxygen therapy. The interquartile ranges of days of invasive mechanical ventilation were 0-3 for patients in the NIV group and 0-5 for patients in the standard oxygen therapy group (P = .05). At 30 days, NIV was associated with significantly more ventilator-free days than standard oxygen therapy (25.4 vs. 23.2; P = .04). At 90 days, 22 patients in the NIV group and 31 patients in the standard oxygen therapy group had died (P = .15).
“Recent high-impact trials have demonstrated the benefits in nonsurgical hypoxemic respiratory failure or equivalence of high-flow nasal cannula compared with NIV in patients after cardiothoracic surgery with moderate to severe hypoxemia. Future studies comparing use of high-flow oxygen cannula vs standard oxygen therapy and NIV for patients after abdominal surgery as preventive (prophylactic) or curative applications are needed,” according to Dr. Jaber and his colleagues.
The primary outcome measure for the study of patients receiving high-flow oxygen therapy was reintubation within 72 hours after extubation; this occurred in fewer patients in the high-flow oxygen group than in the conventional therapy group (13 or 4.9% vs. 32 or 12.2%.) This statistically significant difference was mainly attributable to a lower incidence of respiratory-related reintubation in the high-flow group, compared with the conventional therapy group (1.5% vs. 8.7%), said Dr. Hernandez and his colleagues.
Secondary outcome measures included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, ICU and hospital length of stay and mortality, time to reintubation, and adverse effects. Postintubation respiratory failure was less common in the high-flow therapy group than in the conventional therapy group (22 patients or 8.3% vs. 38 or 14.4%). Differences between the two groups in other secondary outcomes were not statistically significant.
“The main finding of this study was that high-flow oxygen significantly reduced the reintubation rate in critically ill patients at low risk for extubation failure ... High-flow therapy improves oxygenation, and the lower rate of reintubation secondary to hypoxia in the high-flow group corroborates this finding. High-flow oxygen also seems to reduce other causes of respiratory failure such as increased work of breathing and respiratory muscle fatigue, which are frequently associated with reintubation secondary to hypoxia. Another way in which high-flow therapy improves extubation outcome is by conditioning the inspired gas,” said Dr. Hernandez and his colleagues.
No adverse events were reported in either study.
Dr. Hernandez and his colleagues reported no conflicts of interest. Dr. Jaber and his colleagues disclosed no potential conflicts of interest with their study’s sponsors, Montpellier (France) University Hospital and the APARD Foundation.
Dr. Eric Gartman, FCCP, comments: These two studies augment a growing body of literature supporting the use of adjunctive therapies immediately following extubation to prevent reintubation for respiratory failure.
It has been known for several years that the use of noninvasive ventilation (NIV) immediately after extubation in COPD patients prevents reintubation rates, and these new data demonstrate efficacy in an expanded population. Further, the use of high-flow humidified oxygen therapy in acute respiratory failure has been shown to prevent progression to initial intubation, and now these data expand potential use to prevent reintubation, as well.
While not studied, if high-flow oxygen therapy is found to be equivalent to NIV to prevent reintubation (similar to the previously-published prevention of intubation studies), that would be clinically important since there is a significant difference in tolerance to these two therapies. Across these trials, the very important point to remember is that these therapies were found to be effective if put on directly after extubation, and one cannot wait to apply them at the point where the patient shows signs of respiratory decline.
Dr. Eric Gartman, FCCP, comments: These two studies augment a growing body of literature supporting the use of adjunctive therapies immediately following extubation to prevent reintubation for respiratory failure.
It has been known for several years that the use of noninvasive ventilation (NIV) immediately after extubation in COPD patients prevents reintubation rates, and these new data demonstrate efficacy in an expanded population. Further, the use of high-flow humidified oxygen therapy in acute respiratory failure has been shown to prevent progression to initial intubation, and now these data expand potential use to prevent reintubation, as well.
While not studied, if high-flow oxygen therapy is found to be equivalent to NIV to prevent reintubation (similar to the previously-published prevention of intubation studies), that would be clinically important since there is a significant difference in tolerance to these two therapies. Across these trials, the very important point to remember is that these therapies were found to be effective if put on directly after extubation, and one cannot wait to apply them at the point where the patient shows signs of respiratory decline.
Dr. Eric Gartman, FCCP, comments: These two studies augment a growing body of literature supporting the use of adjunctive therapies immediately following extubation to prevent reintubation for respiratory failure.
It has been known for several years that the use of noninvasive ventilation (NIV) immediately after extubation in COPD patients prevents reintubation rates, and these new data demonstrate efficacy in an expanded population. Further, the use of high-flow humidified oxygen therapy in acute respiratory failure has been shown to prevent progression to initial intubation, and now these data expand potential use to prevent reintubation, as well.
While not studied, if high-flow oxygen therapy is found to be equivalent to NIV to prevent reintubation (similar to the previously-published prevention of intubation studies), that would be clinically important since there is a significant difference in tolerance to these two therapies. Across these trials, the very important point to remember is that these therapies were found to be effective if put on directly after extubation, and one cannot wait to apply them at the point where the patient shows signs of respiratory decline.
Extubated patients who either received noninvasive ventilation (NIV) therapy or high-flow nasal cannula oxygen had a lower risk of reintubation, compared with extubated patients who received some form of standard oxygen therapy, according to the results of two multicenter, randomized clinical trials published online in JAMA.
Participants in one of the studies, which included abdominal surgery patients diagnosed with respiratory failure within 7 days following surgery, either received NIV or standard oxygen therapy for 30 days or until ICU discharge, whichever came first. While NIV has been effectively used to treat nonsurgical patients with acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema, there is no evidence to support the use of NIV in surgical patients with hypoxemic acute respiratory failure after abdominal surgery, according to Dr. Samir Jaber of the Saint Eloi University Hospital and Montpellier School of Medicine, both in Montpellier, France, and his colleagues (JAMA. 2016 Apr 5;315[13]:1345-53).
The second study included adult patients who had received mechanical ventilation for more than 12 hours and who met criteria for being considered at low risk for reintubation. Patients were administered either high-flow oxygen therapy through nasal cannula immediately after extubation or continuous conventional oxygen therapy through nasal cannula or nonrebreather facemask; the patients were observed for 72 hours. High-flow therapy has been shown to improve oxygenation and survival in clinical studies of critically ill patients in the acute phase of respiratory failure. “[A study by S.M. Maggiore and his colleagues (Am J Respir Crit Care Med. 2014;190(3):282-8)] suggested that high-flow therapy after planned extubation decreased the reintubation rate in a general population of critical patients, but the benefits might be mainly attributable to improvements in high-risk patients,” said Dr. Gonzalo Hernandez, of the Hospital Virgen de la Salud, Toledo, Spain, and his colleagues (JAMA. 2016 Apr 5;315[13]:1354-61).
In the first study, 148 patients received NIV and 145 patients received standard oxygen therapy only. NIV was administered through a facemask connected to an ICU- or a NIV-dedicated ventilator, using either a heated humidifier or heat and moisture exchanger to warm and humidify inspired gases. Patients were encouraged to use NIV for 6 hours during the first 24 hours of the study and received standard oxygen therapy at a rate of up to 15 L/minute to maintain an arterial oxygen saturation estimate (SpO2) of at least 94% in between NIV sessions. NIV was started at an inspiratory positive airway pressure of 5 cm H2O, increasing to a maximum inspiratory pressure of 15 cm H2O, aiming to achieve an expiratory tidal volume between 6 and 8 mL/kg of predicted body weight and a respiratory rate lower than 25/min. The patients in this study’s control group only received the standard oxygen therapy.
In the other study, 263 patients received conventional therapy, with the oxygen flow having been adjusted to maintain an arterial oxygen saturation estimate of greater than 92%. This study’s other 264 patients received high-flow oxygen therapy, with the flow having been initially set at 10 L/min and titrated upward in 5-L/min steps until patients experienced discomfort. The high-flow therapy was stopped after 24 hours and was followed by conventional oxygen therapy, when needed.
The primary outcome measure in the study involving NIV was cause for reintubation within 7 days of randomization.
Secondary outcome measures included gas exchange, healthcare-associated infection rate within 30 days, number of ventilator-free days between days 1 and 30, antibiotic use duration, ICU and in-hospital length of stay, and 30- and 90-day mortality.
Reintubation occurred in 49 patients in the NIV group and 66 patients in the standard oxygen therapy group, a significant difference (P = .03). Among the reintubated patients, those who had received NIV spent less time under invasive mechanical ventilation as did the patients given standard oxygen therapy. The interquartile ranges of days of invasive mechanical ventilation were 0-3 for patients in the NIV group and 0-5 for patients in the standard oxygen therapy group (P = .05). At 30 days, NIV was associated with significantly more ventilator-free days than standard oxygen therapy (25.4 vs. 23.2; P = .04). At 90 days, 22 patients in the NIV group and 31 patients in the standard oxygen therapy group had died (P = .15).
“Recent high-impact trials have demonstrated the benefits in nonsurgical hypoxemic respiratory failure or equivalence of high-flow nasal cannula compared with NIV in patients after cardiothoracic surgery with moderate to severe hypoxemia. Future studies comparing use of high-flow oxygen cannula vs standard oxygen therapy and NIV for patients after abdominal surgery as preventive (prophylactic) or curative applications are needed,” according to Dr. Jaber and his colleagues.
The primary outcome measure for the study of patients receiving high-flow oxygen therapy was reintubation within 72 hours after extubation; this occurred in fewer patients in the high-flow oxygen group than in the conventional therapy group (13 or 4.9% vs. 32 or 12.2%.) This statistically significant difference was mainly attributable to a lower incidence of respiratory-related reintubation in the high-flow group, compared with the conventional therapy group (1.5% vs. 8.7%), said Dr. Hernandez and his colleagues.
Secondary outcome measures included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, ICU and hospital length of stay and mortality, time to reintubation, and adverse effects. Postintubation respiratory failure was less common in the high-flow therapy group than in the conventional therapy group (22 patients or 8.3% vs. 38 or 14.4%). Differences between the two groups in other secondary outcomes were not statistically significant.
“The main finding of this study was that high-flow oxygen significantly reduced the reintubation rate in critically ill patients at low risk for extubation failure ... High-flow therapy improves oxygenation, and the lower rate of reintubation secondary to hypoxia in the high-flow group corroborates this finding. High-flow oxygen also seems to reduce other causes of respiratory failure such as increased work of breathing and respiratory muscle fatigue, which are frequently associated with reintubation secondary to hypoxia. Another way in which high-flow therapy improves extubation outcome is by conditioning the inspired gas,” said Dr. Hernandez and his colleagues.
No adverse events were reported in either study.
Dr. Hernandez and his colleagues reported no conflicts of interest. Dr. Jaber and his colleagues disclosed no potential conflicts of interest with their study’s sponsors, Montpellier (France) University Hospital and the APARD Foundation.
Extubated patients who either received noninvasive ventilation (NIV) therapy or high-flow nasal cannula oxygen had a lower risk of reintubation, compared with extubated patients who received some form of standard oxygen therapy, according to the results of two multicenter, randomized clinical trials published online in JAMA.
Participants in one of the studies, which included abdominal surgery patients diagnosed with respiratory failure within 7 days following surgery, either received NIV or standard oxygen therapy for 30 days or until ICU discharge, whichever came first. While NIV has been effectively used to treat nonsurgical patients with acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema, there is no evidence to support the use of NIV in surgical patients with hypoxemic acute respiratory failure after abdominal surgery, according to Dr. Samir Jaber of the Saint Eloi University Hospital and Montpellier School of Medicine, both in Montpellier, France, and his colleagues (JAMA. 2016 Apr 5;315[13]:1345-53).
The second study included adult patients who had received mechanical ventilation for more than 12 hours and who met criteria for being considered at low risk for reintubation. Patients were administered either high-flow oxygen therapy through nasal cannula immediately after extubation or continuous conventional oxygen therapy through nasal cannula or nonrebreather facemask; the patients were observed for 72 hours. High-flow therapy has been shown to improve oxygenation and survival in clinical studies of critically ill patients in the acute phase of respiratory failure. “[A study by S.M. Maggiore and his colleagues (Am J Respir Crit Care Med. 2014;190(3):282-8)] suggested that high-flow therapy after planned extubation decreased the reintubation rate in a general population of critical patients, but the benefits might be mainly attributable to improvements in high-risk patients,” said Dr. Gonzalo Hernandez, of the Hospital Virgen de la Salud, Toledo, Spain, and his colleagues (JAMA. 2016 Apr 5;315[13]:1354-61).
In the first study, 148 patients received NIV and 145 patients received standard oxygen therapy only. NIV was administered through a facemask connected to an ICU- or a NIV-dedicated ventilator, using either a heated humidifier or heat and moisture exchanger to warm and humidify inspired gases. Patients were encouraged to use NIV for 6 hours during the first 24 hours of the study and received standard oxygen therapy at a rate of up to 15 L/minute to maintain an arterial oxygen saturation estimate (SpO2) of at least 94% in between NIV sessions. NIV was started at an inspiratory positive airway pressure of 5 cm H2O, increasing to a maximum inspiratory pressure of 15 cm H2O, aiming to achieve an expiratory tidal volume between 6 and 8 mL/kg of predicted body weight and a respiratory rate lower than 25/min. The patients in this study’s control group only received the standard oxygen therapy.
In the other study, 263 patients received conventional therapy, with the oxygen flow having been adjusted to maintain an arterial oxygen saturation estimate of greater than 92%. This study’s other 264 patients received high-flow oxygen therapy, with the flow having been initially set at 10 L/min and titrated upward in 5-L/min steps until patients experienced discomfort. The high-flow therapy was stopped after 24 hours and was followed by conventional oxygen therapy, when needed.
The primary outcome measure in the study involving NIV was cause for reintubation within 7 days of randomization.
Secondary outcome measures included gas exchange, healthcare-associated infection rate within 30 days, number of ventilator-free days between days 1 and 30, antibiotic use duration, ICU and in-hospital length of stay, and 30- and 90-day mortality.
Reintubation occurred in 49 patients in the NIV group and 66 patients in the standard oxygen therapy group, a significant difference (P = .03). Among the reintubated patients, those who had received NIV spent less time under invasive mechanical ventilation as did the patients given standard oxygen therapy. The interquartile ranges of days of invasive mechanical ventilation were 0-3 for patients in the NIV group and 0-5 for patients in the standard oxygen therapy group (P = .05). At 30 days, NIV was associated with significantly more ventilator-free days than standard oxygen therapy (25.4 vs. 23.2; P = .04). At 90 days, 22 patients in the NIV group and 31 patients in the standard oxygen therapy group had died (P = .15).
“Recent high-impact trials have demonstrated the benefits in nonsurgical hypoxemic respiratory failure or equivalence of high-flow nasal cannula compared with NIV in patients after cardiothoracic surgery with moderate to severe hypoxemia. Future studies comparing use of high-flow oxygen cannula vs standard oxygen therapy and NIV for patients after abdominal surgery as preventive (prophylactic) or curative applications are needed,” according to Dr. Jaber and his colleagues.
The primary outcome measure for the study of patients receiving high-flow oxygen therapy was reintubation within 72 hours after extubation; this occurred in fewer patients in the high-flow oxygen group than in the conventional therapy group (13 or 4.9% vs. 32 or 12.2%.) This statistically significant difference was mainly attributable to a lower incidence of respiratory-related reintubation in the high-flow group, compared with the conventional therapy group (1.5% vs. 8.7%), said Dr. Hernandez and his colleagues.
Secondary outcome measures included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, ICU and hospital length of stay and mortality, time to reintubation, and adverse effects. Postintubation respiratory failure was less common in the high-flow therapy group than in the conventional therapy group (22 patients or 8.3% vs. 38 or 14.4%). Differences between the two groups in other secondary outcomes were not statistically significant.
“The main finding of this study was that high-flow oxygen significantly reduced the reintubation rate in critically ill patients at low risk for extubation failure ... High-flow therapy improves oxygenation, and the lower rate of reintubation secondary to hypoxia in the high-flow group corroborates this finding. High-flow oxygen also seems to reduce other causes of respiratory failure such as increased work of breathing and respiratory muscle fatigue, which are frequently associated with reintubation secondary to hypoxia. Another way in which high-flow therapy improves extubation outcome is by conditioning the inspired gas,” said Dr. Hernandez and his colleagues.
No adverse events were reported in either study.
Dr. Hernandez and his colleagues reported no conflicts of interest. Dr. Jaber and his colleagues disclosed no potential conflicts of interest with their study’s sponsors, Montpellier (France) University Hospital and the APARD Foundation.
FROM JAMA
Key clinical point: Extubated patients who either received noninvasive ventilation (NIV) therapy or high-flow nasal cannula oxygen reduced their risk of reintubation, compared with patients who received some form of standard oxygen therapy.
Major finding: In one study, significantly fewer of the patients who received NIV needed to be reintubated than the patients who received standard oxygen therapy.
Data source: Two multicenter, randomized clinical trials published online in JAMA.
Disclosures: Dr. Hernandez and his colleagues reported no conflicts of interest. Dr. Jaber and his colleagues disclosed no potential conflicts of interest with Montpellier (France) University Hospital and the APARD Foundation, who funded their study.
Analysis shows antacids do not slow IPF progression
Idiopathic pulmonary fibrosis (IPF) progressed at similar rates in patients who did and did not receive antacid therapy, based on a post hoc analysis of 52-week data from patients in three placebo-controlled trials.
“We found no association between antacid therapy and progression-free survival, mortality, or adverse events, reported Dr. Michael Krueter of the University of Heidelberg, Germany, and his colleagues (Lancet Respir Med. 2016 Mar 31;S2213-2600[16]00067-9). Further, patients who took antacids and had less than 70% forced vital capacity (FVC) had higher rates of pulmonary and nonpulmonary infections than did patients who did not receive antacid therapy.
“Long-term double-blind randomized studies are urgently needed to further investigate the potential benefit (and possible harms) of antacid therapy in patients with different stages of IPF, especially those with advanced disease,” the researchers said.
The findings challenge the conditional recommendation for antacid use in the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines on the treatment of IPF. That advice was based on previous retrospective studies that indicated antacid users had slower IPF progression, fewer acute exacerbations, and improved survival compared to patients who did not take antacids.
The new study looked at IPF patients in the placebo groups in three large, phase III trials of pirfenidone. In the placebo groups of those studies, 291 patients were receiving antacid therapy and 333 patients were not receiving antacid therapy at baseline. At 1 year, the rates of disease progression in the placebo group were not significantly different – 38% in the antacid users and 42% in those not using antacids. Disease progression was the composite endpoint of death, an absolute FVC decrease of at least 10%, and a decrease of 50 meters or more in the 6-minute walk distance (6MWD). In both groups of patients, the rates of all-cause mortality were also similar.
The risk of death from IPF at 1 year also was not significantly different; 3.9% for antacid users and 5.2% for those not using antacids.
When patients were grouped on the basis of FVC at baseline – either less than 70% FVC or at least 70% FVC or greater – little or no difference was seen in disease mortality, disease progression, changes in FVC, 6MWD, and all-cause hospital admission between patients who received antacids and those who did not receive antacids at baseline.
Prior to stratification by baseline FVC, the rates of all-cause hospital admissions, gastrointestinal adverse effects, infections, and pulmonary infections were similar for the two groups of patients. At 52 weeks, however, infections and pulmonary infections were significantly higher in patients who received antacid therapy at baseline compared with those patients who did not receive antacids at baseline (74% vs. 62%; P = .0174 and 14% vs. 6%; P = .0214, respectively).
Unlike the patients in the previous retrospective studies, few patients in the placebo arms of the clinical trials had advanced IPF and low FVC, the researchers noted. All had IPF that had been diagnosed within 48 months of entering a trial, no evidence of improvement in disease severity in the year preceding trial entry, a predicted FVC of 50% or more, and a 6MWD of 150 meters or more. Among the patients receiving antacid therapy at baseline, 88% used proton-pump inhibitors, 8% used H2 blockers and 4% used proton-pump inhibitors and H2 blockers. Of the 291 patients receiving antacid therapy, 38 stopped after baseline; of the 333 not receiving antacid therapy, 83 started receiving the therapy after baseline.
Dr. Kreuter disclosed ties with Boehringer Ingelheim and InterMune/Roche. Two coauthors disclosed ties with F. Hoffmann-La Roche, which funded the study: Derek Weycker, Ph.D., reported receiving funding from the company, and Dr. Klaus-Uwe Kirchgaessler is an employee.
Idiopathic pulmonary fibrosis (IPF) progressed at similar rates in patients who did and did not receive antacid therapy, based on a post hoc analysis of 52-week data from patients in three placebo-controlled trials.
“We found no association between antacid therapy and progression-free survival, mortality, or adverse events, reported Dr. Michael Krueter of the University of Heidelberg, Germany, and his colleagues (Lancet Respir Med. 2016 Mar 31;S2213-2600[16]00067-9). Further, patients who took antacids and had less than 70% forced vital capacity (FVC) had higher rates of pulmonary and nonpulmonary infections than did patients who did not receive antacid therapy.
“Long-term double-blind randomized studies are urgently needed to further investigate the potential benefit (and possible harms) of antacid therapy in patients with different stages of IPF, especially those with advanced disease,” the researchers said.
The findings challenge the conditional recommendation for antacid use in the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines on the treatment of IPF. That advice was based on previous retrospective studies that indicated antacid users had slower IPF progression, fewer acute exacerbations, and improved survival compared to patients who did not take antacids.
The new study looked at IPF patients in the placebo groups in three large, phase III trials of pirfenidone. In the placebo groups of those studies, 291 patients were receiving antacid therapy and 333 patients were not receiving antacid therapy at baseline. At 1 year, the rates of disease progression in the placebo group were not significantly different – 38% in the antacid users and 42% in those not using antacids. Disease progression was the composite endpoint of death, an absolute FVC decrease of at least 10%, and a decrease of 50 meters or more in the 6-minute walk distance (6MWD). In both groups of patients, the rates of all-cause mortality were also similar.
The risk of death from IPF at 1 year also was not significantly different; 3.9% for antacid users and 5.2% for those not using antacids.
When patients were grouped on the basis of FVC at baseline – either less than 70% FVC or at least 70% FVC or greater – little or no difference was seen in disease mortality, disease progression, changes in FVC, 6MWD, and all-cause hospital admission between patients who received antacids and those who did not receive antacids at baseline.
Prior to stratification by baseline FVC, the rates of all-cause hospital admissions, gastrointestinal adverse effects, infections, and pulmonary infections were similar for the two groups of patients. At 52 weeks, however, infections and pulmonary infections were significantly higher in patients who received antacid therapy at baseline compared with those patients who did not receive antacids at baseline (74% vs. 62%; P = .0174 and 14% vs. 6%; P = .0214, respectively).
Unlike the patients in the previous retrospective studies, few patients in the placebo arms of the clinical trials had advanced IPF and low FVC, the researchers noted. All had IPF that had been diagnosed within 48 months of entering a trial, no evidence of improvement in disease severity in the year preceding trial entry, a predicted FVC of 50% or more, and a 6MWD of 150 meters or more. Among the patients receiving antacid therapy at baseline, 88% used proton-pump inhibitors, 8% used H2 blockers and 4% used proton-pump inhibitors and H2 blockers. Of the 291 patients receiving antacid therapy, 38 stopped after baseline; of the 333 not receiving antacid therapy, 83 started receiving the therapy after baseline.
Dr. Kreuter disclosed ties with Boehringer Ingelheim and InterMune/Roche. Two coauthors disclosed ties with F. Hoffmann-La Roche, which funded the study: Derek Weycker, Ph.D., reported receiving funding from the company, and Dr. Klaus-Uwe Kirchgaessler is an employee.
Idiopathic pulmonary fibrosis (IPF) progressed at similar rates in patients who did and did not receive antacid therapy, based on a post hoc analysis of 52-week data from patients in three placebo-controlled trials.
“We found no association between antacid therapy and progression-free survival, mortality, or adverse events, reported Dr. Michael Krueter of the University of Heidelberg, Germany, and his colleagues (Lancet Respir Med. 2016 Mar 31;S2213-2600[16]00067-9). Further, patients who took antacids and had less than 70% forced vital capacity (FVC) had higher rates of pulmonary and nonpulmonary infections than did patients who did not receive antacid therapy.
“Long-term double-blind randomized studies are urgently needed to further investigate the potential benefit (and possible harms) of antacid therapy in patients with different stages of IPF, especially those with advanced disease,” the researchers said.
The findings challenge the conditional recommendation for antacid use in the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines on the treatment of IPF. That advice was based on previous retrospective studies that indicated antacid users had slower IPF progression, fewer acute exacerbations, and improved survival compared to patients who did not take antacids.
The new study looked at IPF patients in the placebo groups in three large, phase III trials of pirfenidone. In the placebo groups of those studies, 291 patients were receiving antacid therapy and 333 patients were not receiving antacid therapy at baseline. At 1 year, the rates of disease progression in the placebo group were not significantly different – 38% in the antacid users and 42% in those not using antacids. Disease progression was the composite endpoint of death, an absolute FVC decrease of at least 10%, and a decrease of 50 meters or more in the 6-minute walk distance (6MWD). In both groups of patients, the rates of all-cause mortality were also similar.
The risk of death from IPF at 1 year also was not significantly different; 3.9% for antacid users and 5.2% for those not using antacids.
When patients were grouped on the basis of FVC at baseline – either less than 70% FVC or at least 70% FVC or greater – little or no difference was seen in disease mortality, disease progression, changes in FVC, 6MWD, and all-cause hospital admission between patients who received antacids and those who did not receive antacids at baseline.
Prior to stratification by baseline FVC, the rates of all-cause hospital admissions, gastrointestinal adverse effects, infections, and pulmonary infections were similar for the two groups of patients. At 52 weeks, however, infections and pulmonary infections were significantly higher in patients who received antacid therapy at baseline compared with those patients who did not receive antacids at baseline (74% vs. 62%; P = .0174 and 14% vs. 6%; P = .0214, respectively).
Unlike the patients in the previous retrospective studies, few patients in the placebo arms of the clinical trials had advanced IPF and low FVC, the researchers noted. All had IPF that had been diagnosed within 48 months of entering a trial, no evidence of improvement in disease severity in the year preceding trial entry, a predicted FVC of 50% or more, and a 6MWD of 150 meters or more. Among the patients receiving antacid therapy at baseline, 88% used proton-pump inhibitors, 8% used H2 blockers and 4% used proton-pump inhibitors and H2 blockers. Of the 291 patients receiving antacid therapy, 38 stopped after baseline; of the 333 not receiving antacid therapy, 83 started receiving the therapy after baseline.
Dr. Kreuter disclosed ties with Boehringer Ingelheim and InterMune/Roche. Two coauthors disclosed ties with F. Hoffmann-La Roche, which funded the study: Derek Weycker, Ph.D., reported receiving funding from the company, and Dr. Klaus-Uwe Kirchgaessler is an employee.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Antacids don’t slow the progression of idiopathic pulmonary fibrosis.
Major finding: At 52 weeks, infections and pulmonary infections were significantly higher in patients who received antacid therapy at baseline compared with those patients who did not receive antacids at baseline (74% vs. 62%; P = .0174 and 14% vs. 6%; P = .0214, respectively).
Data source: IPF patients in the placebo groups in three large, phase III trials of pirfenidone; 291 patients were receiving antacid therapy and 333 patients were not receiving antacid therapy at baseline.
Disclosures: Dr. Kreuter disclosed ties with Boehringer Ingelheim and InterMune/Roche. Two coauthors disclosed ties with F. Hoffmann-La Roche, which funded the study: Derek Weycker, Ph.D., reported receiving funding from the company, and Dr. Klaus-Uwe Kirchgaessler is an employee.
Thousands of DNA modifications seen in infants of smoking mothers
The findings of a new, international study of 6,685 mothers and their newborns may explain why certain infant and child health problems frequently have been seen in the offspring of mothers who smoked during pregnancy, Kendall Morgan, Ph.D., wrote in the National Institutes of Health Director’s Blog.
The study, published in the American Journal of Human Genetics, “found significant differences between the epigenetic patterns of babies born to women who smoked during pregnancy and those born to nonsmokers, with many of the differences affecting genes known to play key roles in the development of the lungs, face, and nervous system,” Dr. Morgan wrote in the April 12 blog entry.
Smaller studies show there is evidence that maternal smoking can have epigenetic effects on a fetus. The new research from 13 research cohorts reaffirms and renders this finding more statistically powerful, Dr. Morgan wrote. In the infants of women who smoked every day during pregnancy, the researchers found more than 6,000 places where chemical marks on the DNA differed from those of babies born to mothers who did not smoke during pregnancy. The researchers also observed more than 4,600 epigenetic modifications in the DNA of babies of mothers who self-identified as falling under the broad category of having engaged in “any smoking during pregnancy.”
The genes thought to cause a cleft lip and/or palate were among the others to have been epigenetically modified in the fetuses of women who smoked while pregnant. The study also suggested that thousands of the epigenetic modifications seen affected children until at least age 4 years.
Read the study in the American Journal of Human Genetics (doi: 10.1016/j.ajhg.2016.02.019).
The findings of a new, international study of 6,685 mothers and their newborns may explain why certain infant and child health problems frequently have been seen in the offspring of mothers who smoked during pregnancy, Kendall Morgan, Ph.D., wrote in the National Institutes of Health Director’s Blog.
The study, published in the American Journal of Human Genetics, “found significant differences between the epigenetic patterns of babies born to women who smoked during pregnancy and those born to nonsmokers, with many of the differences affecting genes known to play key roles in the development of the lungs, face, and nervous system,” Dr. Morgan wrote in the April 12 blog entry.
Smaller studies show there is evidence that maternal smoking can have epigenetic effects on a fetus. The new research from 13 research cohorts reaffirms and renders this finding more statistically powerful, Dr. Morgan wrote. In the infants of women who smoked every day during pregnancy, the researchers found more than 6,000 places where chemical marks on the DNA differed from those of babies born to mothers who did not smoke during pregnancy. The researchers also observed more than 4,600 epigenetic modifications in the DNA of babies of mothers who self-identified as falling under the broad category of having engaged in “any smoking during pregnancy.”
The genes thought to cause a cleft lip and/or palate were among the others to have been epigenetically modified in the fetuses of women who smoked while pregnant. The study also suggested that thousands of the epigenetic modifications seen affected children until at least age 4 years.
Read the study in the American Journal of Human Genetics (doi: 10.1016/j.ajhg.2016.02.019).
The findings of a new, international study of 6,685 mothers and their newborns may explain why certain infant and child health problems frequently have been seen in the offspring of mothers who smoked during pregnancy, Kendall Morgan, Ph.D., wrote in the National Institutes of Health Director’s Blog.
The study, published in the American Journal of Human Genetics, “found significant differences between the epigenetic patterns of babies born to women who smoked during pregnancy and those born to nonsmokers, with many of the differences affecting genes known to play key roles in the development of the lungs, face, and nervous system,” Dr. Morgan wrote in the April 12 blog entry.
Smaller studies show there is evidence that maternal smoking can have epigenetic effects on a fetus. The new research from 13 research cohorts reaffirms and renders this finding more statistically powerful, Dr. Morgan wrote. In the infants of women who smoked every day during pregnancy, the researchers found more than 6,000 places where chemical marks on the DNA differed from those of babies born to mothers who did not smoke during pregnancy. The researchers also observed more than 4,600 epigenetic modifications in the DNA of babies of mothers who self-identified as falling under the broad category of having engaged in “any smoking during pregnancy.”
The genes thought to cause a cleft lip and/or palate were among the others to have been epigenetically modified in the fetuses of women who smoked while pregnant. The study also suggested that thousands of the epigenetic modifications seen affected children until at least age 4 years.
Read the study in the American Journal of Human Genetics (doi: 10.1016/j.ajhg.2016.02.019).
FROM THE AMERICAN JOURNAL OF HUMAN GENETICS
FDA grants priority review for additional use of atezolizumab
The Food and Drug Administration has granted priority review for atezolizumab for the treatment of people with locally advanced or metastatic non–small-cell lung cancer expressing the programmed death ligand–1 protein (PD-L1) who progressed on or after platinum-containing chemotherapy.
“In a study of atezolizumab in people with previously treated advanced lung cancer, PD-L1 expression correlated with how well they responded to the medicine,” said Dr. Sandra Horning, chief medical officer and head of global product development for Roche and Genentech, in a press release. “The goal of PD-L1 as a biomarker is to identify people most likely to benefit form atezolizumab alone.”
In February 2015, the FDA also granted the drug breakthrough therapy designation for the treatment of people with non–small-cell lung cancer expressing PD-L1 that progressed during or after standard treatments.
Earlier this year, the FDA granted a priority review of atezolizumab for the treatment of people with locally advanced or metastatic urothelial carcinoma, who had disease progression during or following platinum-based chemotherapy in the metastatic stetting or disease worsening within 12 months of receiving platinum-based chemotherapy before or after surgery.
The Food and Drug Administration has granted priority review for atezolizumab for the treatment of people with locally advanced or metastatic non–small-cell lung cancer expressing the programmed death ligand–1 protein (PD-L1) who progressed on or after platinum-containing chemotherapy.
“In a study of atezolizumab in people with previously treated advanced lung cancer, PD-L1 expression correlated with how well they responded to the medicine,” said Dr. Sandra Horning, chief medical officer and head of global product development for Roche and Genentech, in a press release. “The goal of PD-L1 as a biomarker is to identify people most likely to benefit form atezolizumab alone.”
In February 2015, the FDA also granted the drug breakthrough therapy designation for the treatment of people with non–small-cell lung cancer expressing PD-L1 that progressed during or after standard treatments.
Earlier this year, the FDA granted a priority review of atezolizumab for the treatment of people with locally advanced or metastatic urothelial carcinoma, who had disease progression during or following platinum-based chemotherapy in the metastatic stetting or disease worsening within 12 months of receiving platinum-based chemotherapy before or after surgery.
The Food and Drug Administration has granted priority review for atezolizumab for the treatment of people with locally advanced or metastatic non–small-cell lung cancer expressing the programmed death ligand–1 protein (PD-L1) who progressed on or after platinum-containing chemotherapy.
“In a study of atezolizumab in people with previously treated advanced lung cancer, PD-L1 expression correlated with how well they responded to the medicine,” said Dr. Sandra Horning, chief medical officer and head of global product development for Roche and Genentech, in a press release. “The goal of PD-L1 as a biomarker is to identify people most likely to benefit form atezolizumab alone.”
In February 2015, the FDA also granted the drug breakthrough therapy designation for the treatment of people with non–small-cell lung cancer expressing PD-L1 that progressed during or after standard treatments.
Earlier this year, the FDA granted a priority review of atezolizumab for the treatment of people with locally advanced or metastatic urothelial carcinoma, who had disease progression during or following platinum-based chemotherapy in the metastatic stetting or disease worsening within 12 months of receiving platinum-based chemotherapy before or after surgery.
Students’ hours of physical education fall short of national recommendations
Few states follow the national recommendations for weekly time in physical education at the elementary and middle school levels, and no state follows the recommended rate of physical education participation at the high school level, according to the 2016 update to the Shape of the Nation report.
The report, which is sponsored by Voices for Healthy Kids – a joint initiative of the American Heart Association and Robert Wood Johnson Foundation, and SHAPE, the Society of Health and Physical Educators – was formulated from responses of physical education coordinators in the 50 state education agencies and the District of Columbia to a questionnaire on kindergarten through 12th grade physical education and physical activity requirements. The education coordinators were queried during the winter of 2015-2016.
At the elementary school level, five states – Alabama, Florida, Louisiana, New Jersey, and Oregon – and the District of Columbia require students to participate in physical education for 150 minutes per week, the nationally recommended rate. For middle schoolers, the nationally recommended rate of participation in physical education is 225 minutes per week, which is followed in even fewer parts of the country; Montana, Oregon, and the District of Columbia are its sole adopters. California and Hawaii are the only two states who come close to satisfying the national recommendation of providing high school students with 225 minutes per week of physical education. In California, students in grades 7-12 receive 400 minutes of physical education per 10 school days and, in Hawaii, ninth graders receive 200 minutes of physical education per week.
While most states do not require their schools to follow the nationally recommended hours of weekly physical education for schools, the majority of states require students to participate in some amount of physical education during elementary school, middle school, and high school. State physical education requirements are undermined, though, by the majority of states offering ways for students to get out of participating in a physical education course, the report said. Specifically, more than 31 states allow students to substitute participating – in activities such as Junior Reserve Officer Training Corps, interscholastic sports, marching band, and cheerleading – with earning their required physical education credit. In addition, 15 states allow schools or school districts to apply for a waiver from the state physical education requirements, with “medical purposes” having been the most common reason for granting such an exemption.
“There is a large disparity in state requirements and implementation, affecting children’s ability to engage in and benefit from these [physical education] programs,” the report said. “Physical education improves student wellness and academic outcomes, develops life skills that shape the whole person, encourages smart choices, and cultivates a healthful lifestyle.”
The full report is available for download at www.shapeamerica.org/shapeofthenation.
Few states follow the national recommendations for weekly time in physical education at the elementary and middle school levels, and no state follows the recommended rate of physical education participation at the high school level, according to the 2016 update to the Shape of the Nation report.
The report, which is sponsored by Voices for Healthy Kids – a joint initiative of the American Heart Association and Robert Wood Johnson Foundation, and SHAPE, the Society of Health and Physical Educators – was formulated from responses of physical education coordinators in the 50 state education agencies and the District of Columbia to a questionnaire on kindergarten through 12th grade physical education and physical activity requirements. The education coordinators were queried during the winter of 2015-2016.
At the elementary school level, five states – Alabama, Florida, Louisiana, New Jersey, and Oregon – and the District of Columbia require students to participate in physical education for 150 minutes per week, the nationally recommended rate. For middle schoolers, the nationally recommended rate of participation in physical education is 225 minutes per week, which is followed in even fewer parts of the country; Montana, Oregon, and the District of Columbia are its sole adopters. California and Hawaii are the only two states who come close to satisfying the national recommendation of providing high school students with 225 minutes per week of physical education. In California, students in grades 7-12 receive 400 minutes of physical education per 10 school days and, in Hawaii, ninth graders receive 200 minutes of physical education per week.
While most states do not require their schools to follow the nationally recommended hours of weekly physical education for schools, the majority of states require students to participate in some amount of physical education during elementary school, middle school, and high school. State physical education requirements are undermined, though, by the majority of states offering ways for students to get out of participating in a physical education course, the report said. Specifically, more than 31 states allow students to substitute participating – in activities such as Junior Reserve Officer Training Corps, interscholastic sports, marching band, and cheerleading – with earning their required physical education credit. In addition, 15 states allow schools or school districts to apply for a waiver from the state physical education requirements, with “medical purposes” having been the most common reason for granting such an exemption.
“There is a large disparity in state requirements and implementation, affecting children’s ability to engage in and benefit from these [physical education] programs,” the report said. “Physical education improves student wellness and academic outcomes, develops life skills that shape the whole person, encourages smart choices, and cultivates a healthful lifestyle.”
The full report is available for download at www.shapeamerica.org/shapeofthenation.
Few states follow the national recommendations for weekly time in physical education at the elementary and middle school levels, and no state follows the recommended rate of physical education participation at the high school level, according to the 2016 update to the Shape of the Nation report.
The report, which is sponsored by Voices for Healthy Kids – a joint initiative of the American Heart Association and Robert Wood Johnson Foundation, and SHAPE, the Society of Health and Physical Educators – was formulated from responses of physical education coordinators in the 50 state education agencies and the District of Columbia to a questionnaire on kindergarten through 12th grade physical education and physical activity requirements. The education coordinators were queried during the winter of 2015-2016.
At the elementary school level, five states – Alabama, Florida, Louisiana, New Jersey, and Oregon – and the District of Columbia require students to participate in physical education for 150 minutes per week, the nationally recommended rate. For middle schoolers, the nationally recommended rate of participation in physical education is 225 minutes per week, which is followed in even fewer parts of the country; Montana, Oregon, and the District of Columbia are its sole adopters. California and Hawaii are the only two states who come close to satisfying the national recommendation of providing high school students with 225 minutes per week of physical education. In California, students in grades 7-12 receive 400 minutes of physical education per 10 school days and, in Hawaii, ninth graders receive 200 minutes of physical education per week.
While most states do not require their schools to follow the nationally recommended hours of weekly physical education for schools, the majority of states require students to participate in some amount of physical education during elementary school, middle school, and high school. State physical education requirements are undermined, though, by the majority of states offering ways for students to get out of participating in a physical education course, the report said. Specifically, more than 31 states allow students to substitute participating – in activities such as Junior Reserve Officer Training Corps, interscholastic sports, marching band, and cheerleading – with earning their required physical education credit. In addition, 15 states allow schools or school districts to apply for a waiver from the state physical education requirements, with “medical purposes” having been the most common reason for granting such an exemption.
“There is a large disparity in state requirements and implementation, affecting children’s ability to engage in and benefit from these [physical education] programs,” the report said. “Physical education improves student wellness and academic outcomes, develops life skills that shape the whole person, encourages smart choices, and cultivates a healthful lifestyle.”
The full report is available for download at www.shapeamerica.org/shapeofthenation.
FDA Requires Labeling Changes to Metformin-containing Drugs
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
FDA requires labeling changes to metformin-containing drugs
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function, according to the FDA’s recent review of several medical studies.
These findings have prompted the FDA to require manufacturers to change the labeling for metformin-containing drugs. These drugs’ labels now must include the results of the medical studies and new measures of kidney function for determining if a patient can use metformin, says a written statement from the FDA.
Metformin’s current labeling strongly recommends against its use in some patients with kidneys that do not work normally. The FDA is specifically requiring that new labels include the recommendation that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (that is, the glomerular filtration rate estimating equation, eGFR).
The full labeling recommendations are available in the FDA’s written statement.
Additional information including a data summary and a list of metformin-containing drugs is available in the FDA Drug Safety Communication.
The FDA asks that healthcare professionals and patients report adverse events or side effects related to the use of metformin-containing drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
