Mary Ann Moon

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

The measles-mumps-rubella vaccine did not raise the risk of developing autism spectrum disorders in a large, diverse, national cohort of children, even among those who had older siblings with autism and thus were at increased risk, according to a report published online April 21 in JAMA.

To examine a possible association between the MMR vaccine and autism, investigators performed a retrospective cohort study using the claims database for a national health plan that treated more than 34 million patients each year. The geographically diverse study population included 95,727 children born in 2001-2007 who had an older sibling and were enrolled for at least 5 years, said Dr. Anjali Jain of the Lewin Group, Falls Church, Va., a health care consulting firm, and her associates.

©Enterline Design Services LLC/thinkstockphotos.com

A total of 1,929 of these study participants (2.01%) had an older sibling with an autism spectrum disorder (ASD). The prevalence of ASD was 1.04% in the entire study sample, which is comparable with the estimated prevalence of 1.5% in the general U.S. population. Among study participants whose older sibling had ASD, the prevalence of the disorder was 6.9%, which is comparable with the estimated prevalence of 6.4%-24.7% in younger siblings of autistic children in the general U.S. population. Vaccination rates were lower among children whose older siblings had ASD, both at age 2 years (73% vs. 84%) and at age 5 years (86% vs. 92%). This pattern has been observed in other studies and is attributed to some parents’ mistaken belief that vaccinations contributed to the older child’s disorder; some of these parents then refuse to vaccinate their younger children.

At age 2 years, the adjusted relative risk of developing ASD for children who received one dose of MMR, compared with those who received no vaccine, was 0.91 among children with unaffected older siblings and 0.76 among those with affected older siblings. Similarly, at age 5 years, the adjusted relative risk of developing ASD for children who received two doses of MMR, compared with those who received no vaccine, was 1.12 in children with unaffected older siblings and 0.56 in those with affected older siblings, the investigators said (JAMA 2015;313:1534-40).

These findings, which were confirmed in several sensitivity analyses of the data, demonstrate that there is no association between either one or two doses of MMR and an increased risk of ASD, even among children at high risk by virtue of having an older sibling with the disorder, Dr. Jain and her associates said.

This study was funded by the National Institute of Mental Health. Dr. Jain and her associates reported ties to UnitedHealth Group, the national health plan that provided the data.

The measles-mumps-rubella vaccine did not raise the risk of developing autism spectrum disorders in a large, diverse, national cohort of children, even among those who had older siblings with autism and thus were at increased risk, according to a report published online April 21 in JAMA.

To examine a possible association between the MMR vaccine and autism, investigators performed a retrospective cohort study using the claims database for a national health plan that treated more than 34 million patients each year. The geographically diverse study population included 95,727 children born in 2001-2007 who had an older sibling and were enrolled for at least 5 years, said Dr. Anjali Jain of the Lewin Group, Falls Church, Va., a health care consulting firm, and her associates.

©Enterline Design Services LLC/thinkstockphotos.com

A total of 1,929 of these study participants (2.01%) had an older sibling with an autism spectrum disorder (ASD). The prevalence of ASD was 1.04% in the entire study sample, which is comparable with the estimated prevalence of 1.5% in the general U.S. population. Among study participants whose older sibling had ASD, the prevalence of the disorder was 6.9%, which is comparable with the estimated prevalence of 6.4%-24.7% in younger siblings of autistic children in the general U.S. population. Vaccination rates were lower among children whose older siblings had ASD, both at age 2 years (73% vs. 84%) and at age 5 years (86% vs. 92%). This pattern has been observed in other studies and is attributed to some parents’ mistaken belief that vaccinations contributed to the older child’s disorder; some of these parents then refuse to vaccinate their younger children.

At age 2 years, the adjusted relative risk of developing ASD for children who received one dose of MMR, compared with those who received no vaccine, was 0.91 among children with unaffected older siblings and 0.76 among those with affected older siblings. Similarly, at age 5 years, the adjusted relative risk of developing ASD for children who received two doses of MMR, compared with those who received no vaccine, was 1.12 in children with unaffected older siblings and 0.56 in those with affected older siblings, the investigators said (JAMA 2015;313:1534-40).

These findings, which were confirmed in several sensitivity analyses of the data, demonstrate that there is no association between either one or two doses of MMR and an increased risk of ASD, even among children at high risk by virtue of having an older sibling with the disorder, Dr. Jain and her associates said.

This study was funded by the National Institute of Mental Health. Dr. Jain and her associates reported ties to UnitedHealth Group, the national health plan that provided the data.

The measles-mumps-rubella vaccine did not raise the risk of developing autism spectrum disorders in a large, diverse, national cohort of children, even among those who had older siblings with autism and thus were at increased risk, according to a report published online April 21 in JAMA.

To examine a possible association between the MMR vaccine and autism, investigators performed a retrospective cohort study using the claims database for a national health plan that treated more than 34 million patients each year. The geographically diverse study population included 95,727 children born in 2001-2007 who had an older sibling and were enrolled for at least 5 years, said Dr. Anjali Jain of the Lewin Group, Falls Church, Va., a health care consulting firm, and her associates.

©Enterline Design Services LLC/thinkstockphotos.com

A total of 1,929 of these study participants (2.01%) had an older sibling with an autism spectrum disorder (ASD). The prevalence of ASD was 1.04% in the entire study sample, which is comparable with the estimated prevalence of 1.5% in the general U.S. population. Among study participants whose older sibling had ASD, the prevalence of the disorder was 6.9%, which is comparable with the estimated prevalence of 6.4%-24.7% in younger siblings of autistic children in the general U.S. population. Vaccination rates were lower among children whose older siblings had ASD, both at age 2 years (73% vs. 84%) and at age 5 years (86% vs. 92%). This pattern has been observed in other studies and is attributed to some parents’ mistaken belief that vaccinations contributed to the older child’s disorder; some of these parents then refuse to vaccinate their younger children.

At age 2 years, the adjusted relative risk of developing ASD for children who received one dose of MMR, compared with those who received no vaccine, was 0.91 among children with unaffected older siblings and 0.76 among those with affected older siblings. Similarly, at age 5 years, the adjusted relative risk of developing ASD for children who received two doses of MMR, compared with those who received no vaccine, was 1.12 in children with unaffected older siblings and 0.56 in those with affected older siblings, the investigators said (JAMA 2015;313:1534-40).

These findings, which were confirmed in several sensitivity analyses of the data, demonstrate that there is no association between either one or two doses of MMR and an increased risk of ASD, even among children at high risk by virtue of having an older sibling with the disorder, Dr. Jain and her associates said.

This study was funded by the National Institute of Mental Health. Dr. Jain and her associates reported ties to UnitedHealth Group, the national health plan that provided the data.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

Apremilast reduced the number and pain of oral ulcers in patients with Behçet’s syndrome in an industry-sponsored phase II trial, according to a report published online April 16 in the New England Journal of Medicine.

“Any new drug that is effective against oral ulcers (the hallmark lesion of Behçet’s syndrome) may be a candidate for the treatment of other aspects of the disease,” said Dr. Gulen Hatemi of Istanbul University Cerrahpasa, and her associates.

Behçet’s syndrome is characterized by inflammation of the small blood vessels and mucocutaneous lesions, including oral ulcers, genital ulcers, papulopustular lesions, and nodular lesions. These can be disabling and have a substantial negative impact on quality of life. Apremilast is an oral inhibitor of phosphodiesterase-4 that acts on several different inflammatory pathways, has recently been approved for use in psoriasis and psoriatic arthritis, and appears to be a promising treatment for other chronic inflammatory conditions.

The investigators assessed the agent’s efficacy against Behçet’s syndrome in a double-blind trial in which 111 adults at three university hospitals in Turkey and three in the United States were randomly assigned to receive oral apremilast or a matching placebo twice daily for 12 weeks. All the study participants then were given apremilast for a further 12 weeks, after which all were observed during a 4-week follow-up phase with no treatment.

All the study participants had at least two oral ulcers at baseline. The primary efficacy endpoint was the mean number of oral ulcers at week 12. This was significantly lower in the apremilast group (0.5) than in the placebo group (2.1). The median number of oral ulcers also was significantly different, at 0 (range, 0-6) for apremilast and 2 (range, 0-13) for placebo. Apremilast induced improvement within 2 weeks; that effect was sustained throughout the entire 24-week treatment phase of the study and reverted when the drug was discontinued, according to Dr. Hatemi and her associates (N. Engl. J. Med. 2015 April 16 [doi:10.1056/NEJMoa1408684]).

On a scale of 1-100, mean pain scores at baseline were 54.3 in the apremilast group and 51.2 in the placebo group. By week 12, these scores declined significantly with apremilast by 44.7 points, compared with only 16 points for placebo. At week 24, pain scores remained low in the patients who received apremilast throughout the study, and declined by a similar degree (–42.2 points) in those who switched from placebo to apremilast.

In addition, 10 patients in the apremilast group had genital ulcers at baseline, and all were free from genital ulcers at week 12. Several measures of disease activity and quality of life showed significant improvements with apremilast but not with placebo. Adverse events including nausea, diarrhea, vomiting, and fatigue occurred more frequently with apremilast than with placebo.

However, “this was a preliminary study that was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet’s syndrome, or the risk of uncommon serious adverse events,” the investigators noted.

Apremilast reduced the number and pain of oral ulcers in patients with Behçet’s syndrome in an industry-sponsored phase II trial, according to a report published online April 16 in the New England Journal of Medicine.

“Any new drug that is effective against oral ulcers (the hallmark lesion of Behçet’s syndrome) may be a candidate for the treatment of other aspects of the disease,” said Dr. Gulen Hatemi of Istanbul University Cerrahpasa, and her associates.

Behçet’s syndrome is characterized by inflammation of the small blood vessels and mucocutaneous lesions, including oral ulcers, genital ulcers, papulopustular lesions, and nodular lesions. These can be disabling and have a substantial negative impact on quality of life. Apremilast is an oral inhibitor of phosphodiesterase-4 that acts on several different inflammatory pathways, has recently been approved for use in psoriasis and psoriatic arthritis, and appears to be a promising treatment for other chronic inflammatory conditions.

The investigators assessed the agent’s efficacy against Behçet’s syndrome in a double-blind trial in which 111 adults at three university hospitals in Turkey and three in the United States were randomly assigned to receive oral apremilast or a matching placebo twice daily for 12 weeks. All the study participants then were given apremilast for a further 12 weeks, after which all were observed during a 4-week follow-up phase with no treatment.

All the study participants had at least two oral ulcers at baseline. The primary efficacy endpoint was the mean number of oral ulcers at week 12. This was significantly lower in the apremilast group (0.5) than in the placebo group (2.1). The median number of oral ulcers also was significantly different, at 0 (range, 0-6) for apremilast and 2 (range, 0-13) for placebo. Apremilast induced improvement within 2 weeks; that effect was sustained throughout the entire 24-week treatment phase of the study and reverted when the drug was discontinued, according to Dr. Hatemi and her associates (N. Engl. J. Med. 2015 April 16 [doi:10.1056/NEJMoa1408684]).

On a scale of 1-100, mean pain scores at baseline were 54.3 in the apremilast group and 51.2 in the placebo group. By week 12, these scores declined significantly with apremilast by 44.7 points, compared with only 16 points for placebo. At week 24, pain scores remained low in the patients who received apremilast throughout the study, and declined by a similar degree (–42.2 points) in those who switched from placebo to apremilast.

In addition, 10 patients in the apremilast group had genital ulcers at baseline, and all were free from genital ulcers at week 12. Several measures of disease activity and quality of life showed significant improvements with apremilast but not with placebo. Adverse events including nausea, diarrhea, vomiting, and fatigue occurred more frequently with apremilast than with placebo.

However, “this was a preliminary study that was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet’s syndrome, or the risk of uncommon serious adverse events,” the investigators noted.

Apremilast reduced the number and pain of oral ulcers in patients with Behçet’s syndrome in an industry-sponsored phase II trial, according to a report published online April 16 in the New England Journal of Medicine.

“Any new drug that is effective against oral ulcers (the hallmark lesion of Behçet’s syndrome) may be a candidate for the treatment of other aspects of the disease,” said Dr. Gulen Hatemi of Istanbul University Cerrahpasa, and her associates.

Behçet’s syndrome is characterized by inflammation of the small blood vessels and mucocutaneous lesions, including oral ulcers, genital ulcers, papulopustular lesions, and nodular lesions. These can be disabling and have a substantial negative impact on quality of life. Apremilast is an oral inhibitor of phosphodiesterase-4 that acts on several different inflammatory pathways, has recently been approved for use in psoriasis and psoriatic arthritis, and appears to be a promising treatment for other chronic inflammatory conditions.

The investigators assessed the agent’s efficacy against Behçet’s syndrome in a double-blind trial in which 111 adults at three university hospitals in Turkey and three in the United States were randomly assigned to receive oral apremilast or a matching placebo twice daily for 12 weeks. All the study participants then were given apremilast for a further 12 weeks, after which all were observed during a 4-week follow-up phase with no treatment.

All the study participants had at least two oral ulcers at baseline. The primary efficacy endpoint was the mean number of oral ulcers at week 12. This was significantly lower in the apremilast group (0.5) than in the placebo group (2.1). The median number of oral ulcers also was significantly different, at 0 (range, 0-6) for apremilast and 2 (range, 0-13) for placebo. Apremilast induced improvement within 2 weeks; that effect was sustained throughout the entire 24-week treatment phase of the study and reverted when the drug was discontinued, according to Dr. Hatemi and her associates (N. Engl. J. Med. 2015 April 16 [doi:10.1056/NEJMoa1408684]).

On a scale of 1-100, mean pain scores at baseline were 54.3 in the apremilast group and 51.2 in the placebo group. By week 12, these scores declined significantly with apremilast by 44.7 points, compared with only 16 points for placebo. At week 24, pain scores remained low in the patients who received apremilast throughout the study, and declined by a similar degree (–42.2 points) in those who switched from placebo to apremilast.

In addition, 10 patients in the apremilast group had genital ulcers at baseline, and all were free from genital ulcers at week 12. Several measures of disease activity and quality of life showed significant improvements with apremilast but not with placebo. Adverse events including nausea, diarrhea, vomiting, and fatigue occurred more frequently with apremilast than with placebo.

However, “this was a preliminary study that was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet’s syndrome, or the risk of uncommon serious adverse events,” the investigators noted.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.

Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.

They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).

Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.

Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.

After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.

This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.

Among younger patients who underwent mitral valve replacement, 15-year survival was not significantly different between those who received bioprosthetic valves and those who received mechanical devices, based on data from a retrospective study published online April 14 in JAMA.

However, “there is a tradeoff between the incremental risk of reoperation associated with bioprosthetic valves and the greater long-term risk of stroke and major bleeding with mechanical prosthetic valves,” said Dr. Joanna Chikwe of Mount Sinai Hospital, New York, and her associates.

“Even though [our] findings suggest bioprosthetic valve replacement may be a reasonable alternative to mechanical prosthetic valve replacement in patients aged 50-69 years, the 15-year follow-up was insufficient to fully assess lifetime risks, particularly of reoperation,” the researchers noted (JAMA 2015;313:1435-42 [doi:10.1001/jama.2015.3164]).

The choice between bioprosthetic and mechanical mitral valves is controversial in patients younger than 70 years. Bioprosthetics are much more likely to degenerate over time and require reoperation, but mechanical valves put recipients at increased risk of thromboembolism and hemorrhage and require lifelong anticoagulation. In this age group, the use of bioprosthetic devices has steadily and markedly increased in the past decade, from a small fraction of patients to the majority of patients. Yet until now, no large-scale studies have compared long-term survival and other outcomes between the two valves in this patient population.

Dr. Chikwe and her associates reviewed data from a New York state database of all inpatient hospitalizations. They included 3,433 patients aged 50-69 years at baseline who underwent mitral valve replacement with bioprosthetic (23.2%) or mechanical (76.8%) devices from 1997 through 2007. They also assessed a subset of 664 patient pairs who were propensity matched.

After a median follow-up of 8.2 years (maximum, 16.8 years), there was no significant difference in long-term survival between the two groups. Actuarial 15-year survival was 59.9% with bioprosthetic valves and 57.5% with mechanical devices, the investigators said.

This lack of survival difference “refocuses the emphasis” onto major complications and quality of life, the researchers noted. Regarding these secondary outcomes, the incidence of stroke was significantly higher with mechanical mitral valves (14.0% vs 6.8%) and carried a high mortality (8.5%). The incidence of serious bleeding events also was significantly higher with mechanical valves (14.9% vs 9.0%), and also carried a high (7.4%) mortality. Such risks should “be a major consideration in any discussion of prosthesis choice,” Dr. Chikwe and her associates noted.

Conversely, the incidence of mitral valve reoperation was significantly lower with mechanical devices (5.0% vs 11.1%), and related mortality was 5.3%.

These findings differ from those of recent single-center retrospective series, which reported a long-term survival benefit with mechanical valves in younger patients. Those studies, however, were much smaller and had methodological flaws such as failure to control for competing causes of death, the investigators noted.

This study was supported in part by the Mount Sinai School of Medicine, New York, which receives royalties from Edwards Lifesciences and Medtronic for heart valve devices. Dr. Chikwe reported having no relevant financial disclosures; one of her associates reported ties to Medtronic.

Among younger patients who underwent mitral valve replacement, 15-year survival was not significantly different between those who received bioprosthetic valves and those who received mechanical devices, based on data from a retrospective study published online April 14 in JAMA.

However, “there is a tradeoff between the incremental risk of reoperation associated with bioprosthetic valves and the greater long-term risk of stroke and major bleeding with mechanical prosthetic valves,” said Dr. Joanna Chikwe of Mount Sinai Hospital, New York, and her associates.

“Even though [our] findings suggest bioprosthetic valve replacement may be a reasonable alternative to mechanical prosthetic valve replacement in patients aged 50-69 years, the 15-year follow-up was insufficient to fully assess lifetime risks, particularly of reoperation,” the researchers noted (JAMA 2015;313:1435-42 [doi:10.1001/jama.2015.3164]).

The choice between bioprosthetic and mechanical mitral valves is controversial in patients younger than 70 years. Bioprosthetics are much more likely to degenerate over time and require reoperation, but mechanical valves put recipients at increased risk of thromboembolism and hemorrhage and require lifelong anticoagulation. In this age group, the use of bioprosthetic devices has steadily and markedly increased in the past decade, from a small fraction of patients to the majority of patients. Yet until now, no large-scale studies have compared long-term survival and other outcomes between the two valves in this patient population.

Dr. Chikwe and her associates reviewed data from a New York state database of all inpatient hospitalizations. They included 3,433 patients aged 50-69 years at baseline who underwent mitral valve replacement with bioprosthetic (23.2%) or mechanical (76.8%) devices from 1997 through 2007. They also assessed a subset of 664 patient pairs who were propensity matched.

After a median follow-up of 8.2 years (maximum, 16.8 years), there was no significant difference in long-term survival between the two groups. Actuarial 15-year survival was 59.9% with bioprosthetic valves and 57.5% with mechanical devices, the investigators said.

This lack of survival difference “refocuses the emphasis” onto major complications and quality of life, the researchers noted. Regarding these secondary outcomes, the incidence of stroke was significantly higher with mechanical mitral valves (14.0% vs 6.8%) and carried a high mortality (8.5%). The incidence of serious bleeding events also was significantly higher with mechanical valves (14.9% vs 9.0%), and also carried a high (7.4%) mortality. Such risks should “be a major consideration in any discussion of prosthesis choice,” Dr. Chikwe and her associates noted.

Conversely, the incidence of mitral valve reoperation was significantly lower with mechanical devices (5.0% vs 11.1%), and related mortality was 5.3%.

These findings differ from those of recent single-center retrospective series, which reported a long-term survival benefit with mechanical valves in younger patients. Those studies, however, were much smaller and had methodological flaws such as failure to control for competing causes of death, the investigators noted.

This study was supported in part by the Mount Sinai School of Medicine, New York, which receives royalties from Edwards Lifesciences and Medtronic for heart valve devices. Dr. Chikwe reported having no relevant financial disclosures; one of her associates reported ties to Medtronic.

Among younger patients who underwent mitral valve replacement, 15-year survival was not significantly different between those who received bioprosthetic valves and those who received mechanical devices, based on data from a retrospective study published online April 14 in JAMA.

However, “there is a tradeoff between the incremental risk of reoperation associated with bioprosthetic valves and the greater long-term risk of stroke and major bleeding with mechanical prosthetic valves,” said Dr. Joanna Chikwe of Mount Sinai Hospital, New York, and her associates.

“Even though [our] findings suggest bioprosthetic valve replacement may be a reasonable alternative to mechanical prosthetic valve replacement in patients aged 50-69 years, the 15-year follow-up was insufficient to fully assess lifetime risks, particularly of reoperation,” the researchers noted (JAMA 2015;313:1435-42 [doi:10.1001/jama.2015.3164]).

The choice between bioprosthetic and mechanical mitral valves is controversial in patients younger than 70 years. Bioprosthetics are much more likely to degenerate over time and require reoperation, but mechanical valves put recipients at increased risk of thromboembolism and hemorrhage and require lifelong anticoagulation. In this age group, the use of bioprosthetic devices has steadily and markedly increased in the past decade, from a small fraction of patients to the majority of patients. Yet until now, no large-scale studies have compared long-term survival and other outcomes between the two valves in this patient population.

Dr. Chikwe and her associates reviewed data from a New York state database of all inpatient hospitalizations. They included 3,433 patients aged 50-69 years at baseline who underwent mitral valve replacement with bioprosthetic (23.2%) or mechanical (76.8%) devices from 1997 through 2007. They also assessed a subset of 664 patient pairs who were propensity matched.

After a median follow-up of 8.2 years (maximum, 16.8 years), there was no significant difference in long-term survival between the two groups. Actuarial 15-year survival was 59.9% with bioprosthetic valves and 57.5% with mechanical devices, the investigators said.

This lack of survival difference “refocuses the emphasis” onto major complications and quality of life, the researchers noted. Regarding these secondary outcomes, the incidence of stroke was significantly higher with mechanical mitral valves (14.0% vs 6.8%) and carried a high mortality (8.5%). The incidence of serious bleeding events also was significantly higher with mechanical valves (14.9% vs 9.0%), and also carried a high (7.4%) mortality. Such risks should “be a major consideration in any discussion of prosthesis choice,” Dr. Chikwe and her associates noted.

Conversely, the incidence of mitral valve reoperation was significantly lower with mechanical devices (5.0% vs 11.1%), and related mortality was 5.3%.

These findings differ from those of recent single-center retrospective series, which reported a long-term survival benefit with mechanical valves in younger patients. Those studies, however, were much smaller and had methodological flaws such as failure to control for competing causes of death, the investigators noted.

This study was supported in part by the Mount Sinai School of Medicine, New York, which receives royalties from Edwards Lifesciences and Medtronic for heart valve devices. Dr. Chikwe reported having no relevant financial disclosures; one of her associates reported ties to Medtronic.